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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Review Article

Fighting Carcinogenesis with Plant Metabolites by Weakening Proliferative Signaling and Disabling Replicative Immortality Networks of Rapidly Dividing and Invading Cancerous Cells

Author(s): Atif Khurshid Wani, Nahid Akhtar, Arun Sharma and Sally A. El-Zahaby*

Volume 20, Issue 4, 2023

Published on: 22 June, 2022

Page: [371 - 386] Pages: 16

DOI: 10.2174/1567201819666220414085606

Price: $65

Abstract

Background: Cancer, an uncontrolled multistage disease causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction.

Area Covered: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them more effective than the existing cytotoxic regimens.

Expert Opinion: In this context, the current review presented recent data on cancer cases around the globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action of plant-derived compounds, besides explaining the need for improving drug delivery systems.

Keywords: Cancer, proliferative signaling, replicative immortality, plant metabolites, cancer therapy, growth.

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[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[2]
Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther., 2020, 5(1), 28.
[http://dx.doi.org/10.1038/s41392-020-0134-x] [PMID: 32296047]
[3]
West, A.V.; Wullkopf, L.; Christensen, A.; Leijnse, N.; Tarp, J.M.; Mathiesen, J.; Erler, J.T.; Oddershede, L.B. Dynamics of cancerous tissue correlates with invasiveness. Sci. Rep., 2017, 7(1), 43800.
[http://dx.doi.org/10.1038/srep43800] [PMID: 28262796]
[4]
Zavyalova, M.V.; Denisov, E.V.; Tashireva, L.A.; Savelieva, O.E.; Kaigorodova, E.V.; Krakhmal, N.V.; Perelmuter, V.M. Intravasation as a key step in cancer metastasis. Biochemistry (Mosc.), 2019, 84(7), 762-772.
[http://dx.doi.org/10.1134/S0006297919070071] [PMID: 31509727]
[5]
Sasaki, T.; Hiroki, K.; Yamashita, Y. The role of epidermal growth factor receptor in cancer metastasis and microenvironment. BioMed Res. Int., 2013, 2013, 546318.
[http://dx.doi.org/10.1155/2013/546318] [PMID: 23986907]
[6]
Revathidevi, S.; Munirajan, A.K. Akt in cancer: Mediator and more. Semin. Cancer Biol., 2019, 59, 80-91.
[http://dx.doi.org/10.1016/j.semcancer.2019.06.002] [PMID: 31173856]
[7]
Wagner, E.F.; Nebreda, A.R. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer, 2009, 9(8), 537-549.
[http://dx.doi.org/10.1038/nrc2694] [PMID: 19629069]
[8]
Benjamin, D.; Colombi, M.; Moroni, C.; Hall, M.N. Rapamycin passes the torch: A new generation of mTOR inhibitors. Nat. Rev. Drug Discov., 2011, 10(11), 868-880.
[http://dx.doi.org/10.1038/nrd3531] [PMID: 22037041]
[9]
Luga, V.; Zhang, L.; Viloria-Petit, A.M.; Ogunjimi, A.A.; Inanlou, M.R.; Chiu, E.; Buchanan, M.; Hosein, A.N.; Basik, M.; Wrana, J.L. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell, 2012, 151(7), 1542-1556.
[http://dx.doi.org/10.1016/j.cell.2012.11.024] [PMID: 23260141]
[10]
Shen, Q.; Reedijk, M. Notch signaling and the breast cancer microenvironment. Adv. Exp. Med. Biol., 2021, 1287, 183-200.
[http://dx.doi.org/10.1007/978-3-030-55031-8_12] [PMID: 33034033]
[11]
Blake, S.J.; Stannard, K.; Liu, J.; Allen, S.; Yong, M.C.; Mittal, D.; Aguilera, A.R.; Miles, J.J.; Lutzky, V.P.; de Andrade, L.F.; Martinet, L.; Colonna, M.; Takeda, K.; Kühnel, F.; Gurlevik, E.; Bernhardt, G.; Teng, M.W.; Smyth, M.J. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov., 2016, 6(4), 446-459.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0944] [PMID: 26787820]
[12]
Gaillard, H.; García-Muse, T.; Aguilera, A. Replication stress and cancer. Nat. Rev. Cancer, 2015, 15(5), 276-289.
[http://dx.doi.org/10.1038/nrc3916] [PMID: 25907220]
[13]
Aviv, A.; Anderson, J.J.; Shay, J.W. Mutations, cancer and the telomere length paradox. Trends Cancer, 2017, 3(4), 253-258.
[http://dx.doi.org/10.1016/j.trecan.2017.02.005] [PMID: 28718437]
[14]
Wu, L.; Fidan, K.; Um, J.Y.; Ahn, K.S. Telomerase: Key regulator of inflammation and cancer. Pharmacol. Res., 2020, 155, 104726.
[http://dx.doi.org/10.1016/j.phrs.2020.104726] [PMID: 32109579]
[15]
Martino, E.; Casamassima, G.; Castiglione, S.; Cellupica, E.; Pantalone, S.; Papagni, F.; Rui, M.; Siciliano, A.M.; Collina, S. Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead. Bioorg. Med. Chem. Lett., 2018, 28(17), 2816-2826.
[http://dx.doi.org/10.1016/j.bmcl.2018.06.044] [PMID: 30122223]
[16]
Akhtar, N.; Wani, A.K.; Mir, T.U.G. Sapindus mukorossi: Ethnomedicinal uses, phytochemistry, and pharmacological activities. Plant Cell Biotechnol. Mol. Biol., 2021, 300-319.
[17]
Abu Samaan, T.M.; Samec, M.; Liskova, A.; Kubatka, P.; Büsselberg, D. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules, 2019, 9(12), E789.
[http://dx.doi.org/10.3390/biom9120789] [PMID: 31783552]
[18]
Li, Y.; Chen, M.; Yao, B.; Lu, X.; Zhang, X.; He, P.; Vasilatos, S.N.; Ren, X.; Bian, W.; Yao, C. Transferrin receptor-targeted redox/pH-sensitive podophyllotoxin prodrug micelles for multidrug-resistant breast cancer therapy. J. Mater. Chem. B Mater. Biol. Med., 2019, 7(38), 5814-5824.
[http://dx.doi.org/10.1039/C9TB00651F] [PMID: 31495855]
[19]
Mayur, Y.C.; Padma, T.; Parimala, B.H.; Chandramouli, K.H.; Jagadeesh, S.; Gowda, N.M.; Thimmaiah, K.N. Sensitization of multidrug resistant (MDR) cancer cells to vinblastine by novel acridones: Correlation between anti-calmodulin activity and anti-MDR activity. Med. Chem., 2006, 2(1), 63-77.
[http://dx.doi.org/10.2174/157340606775197732] [PMID: 16787357]
[20]
Sheikh-Zeineddini, N.; Safaroghli-Azar, A.; Salari, S.; Bashash, D. C-Myc inhibition sensitizes pre-B ALL cells to the anti-tumor effect of vincristine by altering apoptosis and autophagy: Proposing a probable mechanism of action for 10058-F4. Eur. J. Pharmacol., 2020, 870, 172821.
[http://dx.doi.org/10.1016/j.ejphar.2019.172821] [PMID: 31770526]
[21]
Olsson, M.E.; Gustavsson, K-E.; Andersson, S.; Nilsson, A.; Duan, R.D. Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with antioxidant levels. J. Agric. Food Chem., 2004, 52(24), 7264-7271.
[http://dx.doi.org/10.1021/jf030479p] [PMID: 15563205]
[22]
Olsson, M.E.; Andersson, C.S.; Oredsson, S.; Berglund, R.H.; Gustavsson, K.E. Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries. J. Agric. Food Chem., 2006, 54(4), 1248-1255.
[http://dx.doi.org/10.1021/jf0524776] [PMID: 16478244]
[23]
Garg, S; Devi, S; Sharma, A. An insight into therapeutic profile of lectins in cancer and inflammation. Int. J. Res. Edu. Sci. Methods, 2021, 9(2), 647-654.
[24]
Fridlender, M.; Kapulnik, Y.; Koltai, H. Plant derived substances with anti-cancer activity: From folklore to practice. Front. Plant Sci., 2015, 6, 799.
[http://dx.doi.org/10.3389/fpls.2015.00799] [PMID: 26483815]
[25]
Saleh, K.A.; Albinhassan, T.H.; Elbehairi, S.E.I.; Alshehry, M.A.; Alfaifi, M.Y.; Al-Ghazzawi, A.M.; Al-Kahtani, M.A.; Alasmari, A.D.A. Cell cycle arrest in different cancer cell lines (liver, breast, and colon) induces apoptosis under the influence of the chemical content of Aeluropus lagopoides leaf extracts. Molecules, 2019, 24(3), 507.
[http://dx.doi.org/10.3390/molecules24030507] [PMID: 30708938]
[26]
Ramakrishna, W.; Kumari, A.; Rahman, N.; Mandave, P. Anticancer activities of plant secondary metabolites: Rice callus suspension culture as a new paradigm. Rice Sci., 2021, 28(1), 13-30.
[http://dx.doi.org/10.1016/j.rsci.2020.11.004]
[27]
Fiorentino, S.; Urueña, C.; Lasso, P.; Prieto, K.; Barreto, A. Phyto-immunotherapy, a complementary therapeutic option to decrease metastasis and attack breast cancer stem cells. Front. Oncol., 2020, 10, 1334.
[http://dx.doi.org/10.3389/fonc.2020.01334] [PMID: 32850424]
[28]
Chang, M.Y.; Shieh, D.E.; Chen, C.C.; Yeh, C.S.; Dong, H.P. Linalool induces cell cycle arrest and apoptosis in leukemia cells and cervical cancer cells through CDKIs. Int. J. Mol. Sci., 2015, 16(12), 28169-28179.
[http://dx.doi.org/10.3390/ijms161226089] [PMID: 26703569]
[29]
Durço, A.O.; de Souza, D.S.; Heimfarth, L.; Miguel-Dos-Santos, R.; Rabelo, T.K.; Oliveira Barreto, T.; Rhana, P.; Santos Santana, M.N.; Braga, W.F.; Santos Cruz, J.D.; Lauton-Santos, S.; Santana-Filho, V.J.; Barreto, R.S.S.; Guimarães, A.G.; Alvarez-Leite, J.I.; Quintans Júnior, L.J.; Vasconcelos, C.M.L.; Santos, M.R.V.D.; Barreto, A.S. d-Limonene ameliorates myocardial infarction injury by reducing reactive oxygen species and cell apoptosis in a murine model. J. Nat. Prod., 2019, 82(11), 3010-3019.
[http://dx.doi.org/10.1021/acs.jnatprod.9b00523] [PMID: 31710486]
[30]
Holysz, H.; Lipinska, N.; Paszel-Jaworska, A.; Rubis, B. Telomerase as a useful target in cancer fighting-the breast cancer case. Tumour Biol., 2013, 34(3), 1371-1380.
[http://dx.doi.org/10.1007/s13277-013-0757-4] [PMID: 23558965]
[31]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[32]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[33]
Wong, M.C.S.; Huang, J.; Lok, V.; Wang, J.; Fung, F.; Ding, H.; Zheng, Z.J. Differences in incidence and mortality trends of colorectal cancer worldwide based on sex, age, and anatomic location. Clin. Gastroenterol. Hepatol., 2021, 19(5), 955-966.e61.
[http://dx.doi.org/10.1016/j.cgh.2020.02.026] [PMID: 32088300]
[34]
Araghi, M.; Soerjomataram, I.; Jenkins, M.; Brierley, J.; Morris, E.; Bray, F.; Arnold, M. Global trends in colorectal cancer mortality: Projections to the year 2035. Int. J. Cancer, 2019, 144(12), 2992-3000.
[http://dx.doi.org/10.1002/ijc.32055] [PMID: 30536395]
[35]
Sung, H.; Ferlay, J.; Siegel, R.L. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, caac.21660.
[36]
Miller, K.D.; Fidler-Benaoudia, M.; Keegan, T.H.; Hipp, H.S.; Jemal, A.; Siegel, R.L. Cancer statistics for adolescents and young adults, 2020. CA Cancer J. Clin., 2020, 70(6), 443-459.
[http://dx.doi.org/10.3322/caac.21637] [PMID: 32940362]
[37]
U.S. Breast Cancer Statistics. 2021. Available from: https://www.breastcancer.org/symptoms/understand_bc/statistics [Accessed on 28 Mar 2022].
[38]
Saleem, M.; Ghazali, M.B.; Wahab, M.A.M.A.; Yusoff, N.M.; Mahsin, H.; Seng, C.E.; Khalid, I.A.; Rahman, M.N.G.; Yahaya, B.H. The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients. Adv. Exp. Med. Biol., 2020, 1292, 1-12.
[PMID: 29687286]
[39]
Turkovic, L.; Gurrin, L.C.; Bahlo, M.; Dite, G.S.; Southey, M.C.; Hopper, J.L. Comparing the frequency of common genetic variants and haplotypes between carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian women diagnosed with breast cancer before 40 years of age. BMC Cancer, 2010, 10(1), 466.
[http://dx.doi.org/10.1186/1471-2407-10-466] [PMID: 20807450]
[40]
King, M.C.; Marks, J.H.; Mandell, J.B. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, 2003, 302(5645), 643-646.
[http://dx.doi.org/10.1126/science.1088759] [PMID: 14576434]
[41]
Ward, E.; DeSantis, C.; Robbins, A.; Kohler, B.; Jemal, A. Childhood and adolescent cancer statistics, 2014. CA Cancer J. Clin., 2014, 64(2), 83-103.
[http://dx.doi.org/10.3322/caac.21219] [PMID: 24488779]
[42]
Ward, E.M.; Thun, M.J.; Hannan, L.M.; Jemal, A. Interpreting cancer trends. Ann. N. Y. Acad. Sci., 2006, 1076(1), 29-53.
[http://dx.doi.org/10.1196/annals.1371.048] [PMID: 17119192]
[43]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[44]
Marks, J.S.; Mokdad, A.H.; Town, M. The behavioral risk factor surveillance system: Information, relationships, and influence. Am. J. Prev. Med., 2020, 59(6), 773-775.
[http://dx.doi.org/10.1016/j.amepre.2020.09.001] [PMID: 33220750]
[45]
Thrift, A.P.; Gudenkauf, F.J. Melanoma incidence among non-hispanic whites in all 50 US States from 2001 through 2015. J. Natl. Cancer Inst., 2020, 112(5), 533-539.
[http://dx.doi.org/10.1093/jnci/djz153] [PMID: 31346623]
[46]
Henderson, B.E.; Feigelson, H.S. Hormonal carcinogenesis. Carcinogenesis, 2000, 21(3), 427-433.
[http://dx.doi.org/10.1093/carcin/21.3.427] [PMID: 10688862]
[47]
Protopsaltis, N.J.; Liang, W.; Nudleman, E.; Ferrara, N. Interleukin-22 promotes tumor angiogenesis. Angiogenesis, 2019, 22(2), 311-323.
[http://dx.doi.org/10.1007/s10456-018-9658-x] [PMID: 30539314]
[48]
Pastushenko, I.; Blanpain, C. EMT transition states during tumor progression and metastasis. Trends Cell Biol., 2019, 29(3), 212-226.
[http://dx.doi.org/10.1016/j.tcb.2018.12.001] [PMID: 30594349]
[49]
Bremnes, R.M.; Dønnem, T.; Al-Saad, S.; Al-Shibli, K.; Andersen, S.; Sirera, R.; Camps, C.; Marinez, I.; Busund, L.T. The role of tumor stroma in cancer progression and prognosis: Emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer. J. Thorac. Oncol., 2011, 6(1), 209-217.
[http://dx.doi.org/10.1097/JTO.0b013e3181f8a1bd] [PMID: 21107292]
[50]
Kudo, Y.; Sugimoto, M.; Arias, E.; Kasashima, H.; Cordes, T.; Linares, J.F.; Duran, A.; Nakanishi, Y.; Nakanishi, N.; L’Hermitte, A.; Campos, A.; Senni, N.; Rooslid, T.; Roberts, L.R.; Cuervo, A.M.; Metallo, C.M.; Karin, M.; Diaz-Meco, M.T.; Moscat, J. PKCλ/ι loss induces autophagy, oxidative phosphorylation, and NRF2 to promote liver cancer progression. Cancer Cell, 2020, 38(2), 247-262.e11.
[http://dx.doi.org/10.1016/j.ccell.2020.05.018] [PMID: 32589943]
[51]
Tang, Q.; Chen, J.; Di, Z.; Yuan, W.; Zhou, Z.; Liu, Z.; Han, S.; Liu, Y.; Ying, G.; Shu, X.; Di, M. TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer. J. Exp. Clin. Cancer Res., 2020, 39(1), 232.
[http://dx.doi.org/10.1186/s13046-020-01690-z] [PMID: 33153498]
[52]
Palma, C de S.; Grassi, M.L.; Thomé, C.H.; Ferreira, G.A.; Albuquerque, D.; Pinto, M.T.; Ferreira Melo, F.U.; Kashima, S.; Covas, D.T.; Pitteri, S.J.; Faça, V.M. Proteomic analysis of Epithelial to Mesenchymal Transition (EMT) reveals cross-talk between SNAIL and HDAC1 proteins in breast cancer cells. Mol. Cell. Proteomics, 2016, 15(3), 906-917.
[http://dx.doi.org/10.1074/mcp.M115.052910] [PMID: 26764010]
[53]
Wu, K.; Bonavida, B. The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs. Crit. Rev. Immunol., 2009, 29(3), 241-254.
[http://dx.doi.org/10.1615/CritRevImmunol.v29.i3.40] [PMID: 19538137]
[54]
Casas, E.; Kim, J.; Bendesky, A.; Ohno-Machado, L.; Wolfe, C.J.; Yang, J. Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res., 2011, 71(1), 245-254.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2330] [PMID: 21199805]
[55]
Ostrow, S.L.; Barshir, R.; DeGregori, J.; Yeger-Lotem, E.; Hershberg, R. Cancer evolution is associated with pervasive positive selection on globally expressed genes. PLoS Genet., 2014, 10(3), e1004239.
[http://dx.doi.org/10.1371/journal.pgen.1004239] [PMID: 24603726]
[56]
Ziello, J.E.; Jovin, I.S.; Huang, Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J. Biol. Med., 2007, 80(2), 51-60.
[PMID: 18160990]
[57]
Majmundar, A.J.; Wong, W.J.; Simon, M.C. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell, 2010, 40(2), 294-309.
[http://dx.doi.org/10.1016/j.molcel.2010.09.022] [PMID: 20965423]
[58]
Krieg, M.; Haas, R.; Brauch, H.; Acker, T.; Flamme, I.; Plate, K.H. Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene, 2000, 19(48), 5435-5443.
[http://dx.doi.org/10.1038/sj.onc.1203938] [PMID: 11114720]
[59]
Unterleuthner, D.; Neuhold, P.; Schwarz, K.; Janker, L.; Neuditschko, B.; Nivarthi, H.; Crncec, I.; Kramer, N.; Unger, C.; Hengstschläger, M.; Eferl, R.; Moriggl, R.; Sommergruber, W.; Gerner, C.; Dolznig, H. Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer. Angiogenesis, 2020, 23(2), 159-177.
[http://dx.doi.org/10.1007/s10456-019-09688-8] [PMID: 31667643]
[60]
Vaupel, P.; Schmidberger, H.; Mayer, A. The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. Int. J. Radiat. Biol., 2019, 95(7), 912-919.
[http://dx.doi.org/10.1080/09553002.2019.1589653] [PMID: 30822194]
[61]
Esquivel-Velázquez, M.; Ostoa-Saloma, P.; Palacios-Arreola, M.I.; Nava-Castro, K.E.; Castro, J.I.; Morales-Montor, J. The role of cytokines in breast cancer development and progression. J. Interferon Cytokine Res., 2015, 35(1), 1-16.
[http://dx.doi.org/10.1089/jir.2014.0026] [PMID: 25068787]
[62]
Deshpande, A.; Sicinski, P.; Hinds, P.W. Cyclins and cdks in development and cancer: A perspective. Oncogene, 2005, 24(17), 2909-2915.
[http://dx.doi.org/10.1038/sj.onc.1208618] [PMID: 15838524]
[63]
Sever, R.; Brugge, J.S. Signal transduction in cancer. Cold Spring Harb. Perspect. Med., 2015, 5(4), a006098.
[http://dx.doi.org/10.1101/cshperspect.a006098] [PMID: 25833940]
[64]
Luo, M.; Brooks, M.; Wicha, M.S. Epithelial-mesenchymal plasticity of breast cancer stem cells: Implications for metastasis and therapeutic resistance. Curr. Pharm. Des., 2015, 21(10), 1301-1310.
[http://dx.doi.org/10.2174/1381612821666141211120604] [PMID: 25506895]
[65]
Läsche, M.; Emons, G.; Gründker, C. Shedding new light on cancer metabolism: A metabolic tightrope between life and death. Front. Oncol., 2020, 10, 409.
[http://dx.doi.org/10.3389/fonc.2020.00409] [PMID: 32300553]
[66]
Muz, B.; de la Puente, P.; Azab, F.; Azab, A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl.), 2015, 3, 83-92.
[http://dx.doi.org/10.2147/HP.S93413] [PMID: 27774485]
[67]
Chu, Y.; Chang, Y.; Lu, W.; Sheng, X.; Wang, S.; Xu, H.; Ma, J. Regulation of autophagy by glycolysis in cancer. Cancer Manag. Res., 2020, 12, 13259-13271.
[http://dx.doi.org/10.2147/CMAR.S279672] [PMID: 33380833]
[68]
De Nola, R.; Menga, A.; Castegna, A.; Loizzi, V.; Ranieri, G.; Cicinelli, E.; Cormio, G. The crowded crosstalk between cancer cells and stromal microenvironment in gynecological malignancies: Biological pathways and therapeutic implication. Int. J. Mol. Sci., 2019, 20(10), 2401.
[http://dx.doi.org/10.3390/ijms20102401] [PMID: 31096567]
[69]
Pascut, D.; Pratama, M.Y.; Vo, N.V.T.; Masadah, R.; Tiribelli, C. The crosstalk between tumor cells and the microenvironment in hepatocellular carcinoma: The role of exosomal micrornas and their clinical implications. Cancers (Basel), 2020, 12(4), 823.
[http://dx.doi.org/10.3390/cancers12040823] [PMID: 32235370]
[70]
Godoy, G.; Gakis, G.; Smith, C.L.; Fahmy, O. Effects of androgen and estrogen receptor signaling pathways on bladder cancer initiation and progression. Bladder Cancer, 2016, 2(2), 127-137.
[http://dx.doi.org/10.3233/BLC-160052] [PMID: 27376135]
[71]
Siersbæk, R.; Kumar, S.; Carroll, J.S. Signaling pathways and steroid receptors modulating estrogen receptor α function in breast cancer. Genes Dev., 2018, 32(17-18), 1141-1154.
[http://dx.doi.org/10.1101/gad.316646.118] [PMID: 30181360]
[72]
Glick, D.; Barth, S.; Macleod, K.F. Autophagy: Cellular and molecular mechanisms. J. Pathol., 2010, 221(1), 3-12.
[http://dx.doi.org/10.1002/path.2697] [PMID: 20225336]
[73]
Chun, Y.; Kim, J. Autophagy: An essential degradation program for cellular homeostasis and life. Cells, 2018, 7(12), 278.
[http://dx.doi.org/10.3390/cells7120278] [PMID: 30572663]
[74]
Sarkar, S.; Mirzaei, R.; Zemp, F.J.; Wei, W.; Senger, D.L.; Robbins, S.M.; Yong, V.W. Activation of NOTCH signaling by tenascin-C promotes growth of human brain tumor-initiating cells. Cancer Res., 2017, 77(12), 3231-3243.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2171] [PMID: 28416488]
[75]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[76]
Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull., 2017, 7(3), 339-348.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[77]
Friedl, P.; Wolf, K. Tumour-cell invasion and migration: Diversity and escape mechanisms. Nat. Rev. Cancer, 2003, 3(5), 362-374.
[http://dx.doi.org/10.1038/nrc1075] [PMID: 12724734]
[78]
Sclafani, R.A.; Holzen, T.M. Cell cycle regulation of DNA replication. Annu. Rev. Genet., 2007, 41(1), 237-280.
[http://dx.doi.org/10.1146/annurev.genet.41.110306.130308] [PMID: 17630848]
[79]
Chen, J.H.; Stoeber, K.; Kingsbury, S.; Ozanne, S.E.; Williams, G.H.; Hales, C.N. Loss of proliferative capacity and induction of senescence in oxidatively stressed human fibroblasts. J. Biol. Chem., 2004, 279(47), 49439-49446.
[http://dx.doi.org/10.1074/jbc.M409153200] [PMID: 15377661]
[80]
Liu, X.L.; Ding, J.; Meng, L.H. Oncogene-induced senescence: A double edged sword in cancer. Acta Pharmacol. Sin., 2018, 39(10), 1553-1558.
[http://dx.doi.org/10.1038/aps.2017.198] [PMID: 29620049]
[81]
Suram, A.; Kaplunov, J.; Patel, P.L.; Ruan, H.; Cerutti, A.; Boccardi, V.; Fumagalli, M.; Di Micco, R.; Mirani, N.; Gurung, R.L.; Hande, M.P.; d’Adda di Fagagna, F.; Herbig, U. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J., 2012, 31(13), 2839-2851.
[http://dx.doi.org/10.1038/emboj.2012.132] [PMID: 22569128]
[82]
Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; Abete, P. Oxidative stress, aging, and diseases. Clin. Interv. Aging, 2018, 13, 757-772.
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]
[83]
Chen, J-H.; Hales, C.N.; Ozanne, S.E. DNA damage, cellular senescence and organismal ageing: Causal or correlative? Nucleic Acids Res., 2007, 35(22), 7417-7428.
[http://dx.doi.org/10.1093/nar/gkm681] [PMID: 17913751]
[84]
Cong, Y.S.; Wright, W.E.; Shay, J.W. Human telomerase and its regulation. Microbiol. Mol. Biol. Rev., 2002, 66(3), 407-425.
[http://dx.doi.org/10.1128/MMBR.66.3.407-425.2002] [PMID: 12208997]
[85]
Jafri, M.A.; Ansari, S.A.; Alqahtani, M.H.; Shay, J.W. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med., 2016, 8(1), 69.
[http://dx.doi.org/10.1186/s13073-016-0324-x] [PMID: 27323951]
[86]
Wenz, C.; Enenkel, B.; Amacker, M.; Kelleher, C.; Damm, K.; Lingner, J. Human telomerase contains two cooperating telomerase RNA molecules. EMBO J., 2001, 20(13), 3526-3534.
[http://dx.doi.org/10.1093/emboj/20.13.3526] [PMID: 11432839]
[87]
Napier, C.E.; Veas, L.A.; Kan, C.Y.; Taylor, L.M.; Yuan, J.; Wen, V.W.; James, A.; O’Brien, T.A.; Lock, R.B.; MacKenzie, K.L. Mild hyperoxia limits hTR levels, telomerase activity, and telomere length maintenance in hTERT-transduced bone marrow endothelial cells. Biochim. Biophys. Acta, 2010, 1803(10), 1142-1153.
[http://dx.doi.org/10.1016/j.bbamcr.2010.06.010] [PMID: 20619302]
[88]
Okamoto, K.; Seimiya, H. Revisiting telomere shortening in cancer. Cells, 2019, 8(2), E107.
[http://dx.doi.org/10.3390/cells8020107] [PMID: 30709063]
[89]
Wang, Y.; Sharpless, N.; Chang, S. p16(INK4a) protects against dysfunctional telomere-induced ATR-dependent DNA damage responses. J. Clin. Invest., 2013, 123(10), 4489-4501.
[http://dx.doi.org/10.1172/JCI69574] [PMID: 24091330]
[90]
Chen, J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect. Med., 2016, 6(3), a026104.
[http://dx.doi.org/10.1101/cshperspect.a026104] [PMID: 26931810]
[91]
Floquet, C.; Deforges, J.; Rousset, J.P.; Bidou, L. Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides. Nucleic Acids Res., 2011, 39(8), 3350-3362.
[http://dx.doi.org/10.1093/nar/gkq1277] [PMID: 21149266]
[92]
Duffy, M.J.; Synnott, N.C.; Crown, J. Mutant p53 as a target for cancer treatment. Eur. J. Cancer, 2017, 83(83), 258-265.
[http://dx.doi.org/10.1016/j.ejca.2017.06.023] [PMID: 28756138]
[93]
Kim, R.H.; Kang, M.K.; Kim, T.; Yang, P.; Bae, S.; Williams, D.W.; Phung, S.; Shin, K.H.; Hong, C.; Park, N.H. Regulation of p53 during senescence in normal human keratinocytes. Aging Cell, 2015, 14(5), 838-846.
[http://dx.doi.org/10.1111/acel.12364] [PMID: 26138448]
[94]
Li, W.; Peng, X.; Lang, J.; Xu, C. Targeting mouse double minute 2: Current concepts in DNA damage repair and therapeutic approaches in cancer. Front. Pharmacol., 2020, 11, 631.
[http://dx.doi.org/10.3389/fphar.2020.00631] [PMID: 32477121]
[95]
Li, J.; Wang, S.X. Synergistic enhancement of the antitumor activity of 5-fluorouracil by bornyl acetate in SGC-7901 human gastric cancer cells and the determination of the underlying mechanism of action. J. BUON, 2016, 21(1), 108-117.
[PMID: 27061538]
[96]
Yusof, K.M.; Makpol, S.; Jamal, R.; Harun, R.; Mokhtar, N.; Ngah, W.Z. γ-Tocotrienol and 6-Gingerol in combination synergistically induce cytotoxicity and apoptosis in HT-29 and SW837 human colorectal cancer cells. Molecules, 2015, 20(6), 10280-10297.
[http://dx.doi.org/10.3390/molecules200610280] [PMID: 26046324]
[97]
Keating, E.; Martel, F. Antimetabolic effects of polyphenols in breast cancer cells: Focus on glucose uptake and metabolism. Front. Nutr., 2018, 5, 25.
[http://dx.doi.org/10.3389/fnut.2018.00025] [PMID: 29713632]
[98]
Carvalho, K.C.; Cunha, I.W.; Rocha, R.M.; Ayala, F.R.; Cajaíba, M.M.; Begnami, M.D.; Vilela, R.S.; Paiva, G.R.; Andrade, R.G.; Soares, F.A. GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker. Clinics (São Paulo), 2011, 66(6), 965-972.
[http://dx.doi.org/10.1590/S1807-59322011000600008] [PMID: 21808860]
[99]
Xu, Y.Y.; Wu, T.T.; Zhou, S.H.; Bao, Y.Y.; Wang, Q.Y.; Fan, J.; Huang, Y.P. Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: An in vitro study. Int. J. Clin. Exp. Pathol., 2014, 7(7), 3938-3947.
[PMID: 25120770]
[100]
Brockmueller, A.; Sameri, S.; Liskova, A.; Zhai, K.; Varghese, E.; Samuel, S.M.; Büsselberg, D.; Kubatka, P.; Shakibaei, M. Resveratrol’s anti-cancer effects through the modulation of tumor glucose metabolism. Cancers (Basel), 2021, 13(2), 188.
[http://dx.doi.org/10.3390/cancers13020188] [PMID: 33430318]
[101]
Yang, Y.; Wolfram, J.; Boom, K.; Fang, X.; Shen, H.; Ferrari, M. Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem. Funct., 2013, 31(5), 374-379.
[http://dx.doi.org/10.1002/cbf.2905] [PMID: 23042260]
[102]
Wu, C.H.; Ho, Y.S.; Tsai, C.Y.; Wang, Y.J.; Tseng, H.; Wei, P.L.; Lee, C.H.; Liu, R.S.; Lin, S.Y. In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter. Int. J. Cancer, 2009, 124(9), 2210-2219.
[http://dx.doi.org/10.1002/ijc.24189] [PMID: 19123483]
[103]
Bartrons, R.; Simon-Molas, H.; Rodríguez-García, A.; Castaño, E.; Navarro-Sabaté, À.; Manzano, A.; Martinez-Outschoorn, U.E. Fructose 2,6-bisphosphate in cancer cell metabolism. Front. Oncol., 2018, 8, 331.
[http://dx.doi.org/10.3389/fonc.2018.00331] [PMID: 30234009]
[104]
Shi, L.; Pan, H.; Liu, Z.; Xie, J.; Han, W. Roles of PFKFB3 in cancer. Signal Transduct. Target. Ther., 2017, 2(1), 17044.
[http://dx.doi.org/10.1038/sigtrans.2017.44] [PMID: 29263928]
[105]
Ye, M.; Liu, J.K.; Lu, Z.X.; Zhao, Y.; Liu, S.F.; Li, L.L.; Tan, M.; Weng, X.X.; Li, W.; Cao, Y. Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, inhibits tumor cell growth by inducing apoptosis in vitro. FEBS Lett., 2005, 579(16), 3437-3443.
[http://dx.doi.org/10.1016/j.febslet.2005.05.013] [PMID: 15949805]
[106]
Deng, Q.; Yu, X.; Xiao, L.; Hu, Z.; Luo, X.; Tao, Y.; Yang, L.; Liu, X.; Chen, H.; Ding, Z.; Feng, T.; Tang, Y.; Weng, X.; Gao, J.; Yi, W.; Bode, A.M.; Dong, Z.; Liu, J.; Cao, Y. Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway. Cell Death Dis., 2013, 4(9), e804.
[http://dx.doi.org/10.1038/cddis.2013.324] [PMID: 24052072]
[107]
Talib, W.H.; Mahasneh, A.M. Antiproliferative activity of plant extracts used against cancer in traditional medicine. Sci. Pharm., 2010, 78(1), 33-45.
[http://dx.doi.org/10.3797/scipharm.0912-11] [PMID: 21179373]
[108]
Pei, J.S.; Liu, C.C.; Hsu, Y.N.; Lin, L.L.; Wang, S.C.; Chung, J.G.; Bau, D.T.; Lin, S.S. Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast cancer cells via mitochondria-dependent pathway. In vivo, 2012, 26(6), 963-970.
[PMID: 23160679]
[109]
Wani, A.K.; Akhtar, N. Extraction designs and therapeutic attributes associated with limonene: A review. Plant Arch., 2021, 21, 1608-1620.
[110]
Güllü, N.; Kobelt, D.; Brim, H.; Rahman, S.; Timm, L.; Smith, J.; Soleimani, A.; Di Marco, S.; Bisti, S.; Ashktorab, H.; Stein, U. Saffron crudes and compounds restrict MACC1-dependent cell proliferation and migration of colorectal cancer cells. Cells, 2020, 9(8), E1829.
[http://dx.doi.org/10.3390/cells9081829] [PMID: 32756469]
[111]
Juneja, M.; Kobelt, D.; Walther, W.; Voss, C.; Smith, J.; Specker, E.; Neuenschwander, M.; Gohlke, B.O.; Dahlmann, M.; Radetzki, S.; Preissner, R.; von Kries, J.P.; Schlag, P.M.; Stein, U. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol., 2017, 15(6), e2000784.
[http://dx.doi.org/10.1371/journal.pbio.2000784] [PMID: 28570591]
[112]
Jafari, N.; Zargar, S.J.; Delnavazi, M.R.; Yassa, N. Cell cycle arrest and apoptosis induction of phloroacetophenone glycosides and caffeoylquinic Acid Derivatives in Gastric Adenocarcinoma (AGS) cells. Anticancer. Agents Med. Chem., 2018, 18(4), 610-616.
[http://dx.doi.org/10.2174/1871520618666171219121449] [PMID: 29256356]
[113]
Nepal, M.; Choi, H.J.; Choi, B.Y.; Kim, S.L.; Ryu, J.H.; Kim, D.H.; Lee, Y.H.; Soh, Y. Anti-angiogenic and anti-tumor activity of Bavachinin by targeting hypoxia-inducible factor-1α. Eur. J. Pharmacol., 2012, 691(1-3), 28-37.
[http://dx.doi.org/10.1016/j.ejphar.2012.06.028] [PMID: 22760073]
[114]
Chen, M.C.; Lee, C.F.; Huang, W.H.; Chou, T.C. Magnolol suppresses hypoxia-induced angiogenesis via inhibition of HIF-1α/VEGF signaling pathway in human bladder cancer cells. Biochem. Pharmacol., 2013, 85(9), 1278-1287.
[http://dx.doi.org/10.1016/j.bcp.2013.02.009] [PMID: 23416116]
[115]
Choi, H.J.; Eun, J.S.; Kim, D.K.; Li, R.H.; Shin, T.Y.; Park, H.; Cho, N.P.; Soh, Y. Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1alpha in human osteosarcoma cells. Eur. J. Pharmacol., 2008, 579(1-3), 58-65.
[http://dx.doi.org/10.1016/j.ejphar.2007.10.010] [PMID: 17980359]
[116]
Peng, Y.G.; Zhang, L. Baohuoside-I suppresses cell proliferation and migration by up-regulating miR-144 in melanoma. Pharm. Biol., 2018, 56(1), 43-50.
[http://dx.doi.org/10.1080/13880209.2017.1418391] [PMID: 29260980]
[117]
Fang, L.; Xu, W.; Kong, D. Icariin inhibits cell proliferation, migration and invasion by down-regulation of microRNA-625-3p in thyroid cancer cells. Biomed. Pharmacother., 2019, 109, 2456-2463.
[http://dx.doi.org/10.1016/j.biopha.2018.04.012] [PMID: 30551506]
[118]
Liang, H.X.; Sun, L.B.; Liu, N.J. Neferine inhibits proliferation, migration and invasion of U251 glioma cells by down-regulation of miR-10b. Biomed. Pharmacother., 2019, 109, 1032-1040.
[http://dx.doi.org/10.1016/j.biopha.2018.10.122] [PMID: 30551353]
[119]
Sun, L.; Jin, X.; Xie, L.; Xu, G.; Cui, Y.; Chen, Z. Swainsonine represses glioma cell proliferation, migration and invasion by reduction of miR-92a expression. BMC Cancer, 2019, 19(1), 247.
[http://dx.doi.org/10.1186/s12885-019-5425-7] [PMID: 30890138]
[120]
Xu, D.; Chi, G.; Zhao, C.; Li, D. Ligustrazine inhibits growth, migration and invasion of medulloblastoma daoy cells by up-regulation of miR-211. Cell. Physiol. Biochem., 2018, 49(5), 2012-2021.
[http://dx.doi.org/10.1159/000493712] [PMID: 30244244]
[121]
Huang, B.; Lei, S.; Wang, D.; Sun, Y.; Yin, J. Sulforaphane exerts anticancer effects on human liver cancer cells via induction of apoptosis and inhibition of migration and invasion by targeting MAPK7 signalling pathway. J. BUON, 2021, 26(2), 642.
[PMID: 34077026]
[122]
Yu, L.; Sun, Y.; Su, J.; Li, X. Bismahanine exerts anticancer effects on human cervical cancer cells by inhibition of growth, migration and invasion via suppression of NF-kB signalling pathway. J. BUON, 2021, 26(2), 644.
[PMID: 34077028]
[123]
Shangguan, F.; Zhou, H.; Ma, N.; Wu, S.; Huang, H.; Jin, G.; Wu, S.; Hong, W.; Zhuang, W.; Xia, H.; Lan, L. A novel mechanism of cannabidiol in suppressing hepatocellular carcinoma by inducing GSDME dependent pyroptosis. Front. Cell Dev. Biol., 2021, 9, 697832.
[http://dx.doi.org/10.3389/fcell.2021.697832] [PMID: 34350183]
[124]
Peng, S.Y.; Lin, L.C.; Chen, S.R.; Farooqi, A.A.; Cheng, Y.B.; Tang, J.Y.; Chang, H.W. Pomegranate extract (POMx) induces mitochondrial dysfunction and apoptosis of oral cancer cells. Antioxidants, 2021, 10(7), 1117.
[http://dx.doi.org/10.3390/antiox10071117] [PMID: 34356350]
[125]
Tang, J.Y.; Wu, K.H.; Wang, Y.Y.; Farooqi, A.A.; Huang, H.W.; Yuan, S.F.; Jian, R.I.; Tsao, L.Y.; Chen, P.A.; Chang, F.R.; Cheng, Y.B.; Hu, H.C.; Chang, H.W. Methanol extract of Usnea barbata induces cell killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress. Antioxidants, 2020, 9(8), E694.
[http://dx.doi.org/10.3390/antiox9080694] [PMID: 32756347]
[126]
Sankaranarayanan, R.; Valiveti, C.K.; Kumar, D.R.; Van Slambrouck, S.; Kesharwani, S.S.; Seefeldt, T.; Scaria, J.; Tummala, H.; Bhat, G.J. The flavonoid metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK inhibitor and an anti-proliferative agent: A potential role in cancer prevention. Cancers (Basel), 2019, 11(3), E427.
[http://dx.doi.org/10.3390/cancers11030427] [PMID: 30917530]
[127]
Carraz, M.; Lavergne, C.; Jullian, V.; Wright, M.; Gairin, J.E.; Gonzales de la Cruz, M.; Bourdy, G. Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells. J. Ethnopharmacol., 2015, 166, 185-199.
[http://dx.doi.org/10.1016/j.jep.2015.02.028] [PMID: 25701751]
[128]
Wu, B.; Zhang, Q.; Shen, W.; Zhu, J. Anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cell line. Mol. Cell. Biochem., 2008, 313(1-2), 125-132.
[http://dx.doi.org/10.1007/s11010-008-9749-x] [PMID: 18398671]
[129]
Farooqi, A.A.; Butt, G.; El-Zahaby, S.A.; Attar, R.; Sabitaliyevich, U.Y.; Jovic, J.J.; Tang, K.F.; Naureen, H.; Xu, B. Luteolin mediated targeting of protein network and microRNAs in different cancers: Focus on JAK-STAT, NOTCH, mTOR and TRAIL-mediated signaling pathways. Pharmacol. Res., 2020, 160, 105188.
[http://dx.doi.org/10.1016/j.phrs.2020.105188] [PMID: 32919041]
[130]
Auyeung, K.K.; Woo, P.K.; Law, P.C.; Ko, J.K. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J. Ethnopharmacol., 2012, 141(2), 635-641.
[http://dx.doi.org/10.1016/j.jep.2011.08.010] [PMID: 21864667]
[131]
Chen, W.; Zhang, Y.; Gu, X.; Qian, P.; Liu, W.; Shu, P. Qi Ling decoction reduces gastric cancer cell metastasis by inhibiting MMP-9 through the PI3K/Akt signaling pathway. Am. J. Transl. Res., 2021, 13(5), 4591-4602.
[PMID: 34150039]
[132]
Li, C.; Qin, Y.; Zhong, Y.; Qin, Y.; Wei, Y.; Li, L.; Xie, Y. Fentanyl inhibits the progression of gastric cancer through the suppression of MMP-9 via the PI3K/Akt signaling pathway. Ann. Transl. Med., 2020, 8(4), 118.
[http://dx.doi.org/10.21037/atm.2019.12.161] [PMID: 32175411]
[133]
Yang, Z.P.; Zhao, Y.; Huang, F.; Chen, J.; Yao, Y.H.; Li, J.; Wu, X.N. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway. World J. Gastroenterol., 2015, 21(36), 10385-10399.
[http://dx.doi.org/10.3748/wjg.v21.i36.10385] [PMID: 26420965]
[134]
Saleem, M.; Asif, J.; Asif, M.; Saleem, U. Amygdalin from apricot kernels induces apoptosis and causes cell cycle arrest in cancer cells: An updated review. Anticancer. Agents Med. Chem., 2018, 18(12), 1650-1655.
[http://dx.doi.org/10.2174/1871520618666180105161136] [PMID: 29308747]
[135]
Zheng, Y.B.; Xiao, G.C.; Tong, S.L.; Ding, Y.; Wang, Q.S.; Li, S.B.; Hao, Z.N. Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling. World J. Gastroenterol., 2015, 21(23), 7197-7207.
[http://dx.doi.org/10.3748/wjg.v21.i23.7197] [PMID: 26109806]
[136]
Zang, Y.Q.; Feng, Y.Y.; Luo, Y.H.; Zhai, Y.Q.; Ju, X.Y.; Feng, Y.C.; Wang, J.R.; Yu, C.Q.; Jin, C.H. Glycitein induces reactive oxygen species-dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF-κB pathway in human gastric cancer cells. Drug Dev. Res., 2019, 80(5), 573-584.
[http://dx.doi.org/10.1002/ddr.21534] [PMID: 30916421]
[137]
Shay, J.W. Role of telomeres and telomerase in aging and cancer. Cancer Discov., 2016, 6(6), 584-593.
[http://dx.doi.org/10.1158/2159-8290.CD-16-0062] [PMID: 27029895]
[138]
Ganesan, K.; Xu, B. Telomerase inhibitors from natural products and their anticancer potential. Int. J. Mol. Sci., 2017, 19(1), 13.
[http://dx.doi.org/10.3390/ijms19010013] [PMID: 29267203]
[139]
Zhou, D.H.; Wang, X.; Yang, M.; Shi, X.; Huang, W.; Feng, Q. Combination of low concentration of (-)-epigallocatechin gallate (EGCG) and curcumin strongly suppresses the growth of non-small cell lung cancer in vitro and in vivo through causing cell cycle arrest. Int. J. Mol. Sci., 2013, 14(6), 12023-12036.
[http://dx.doi.org/10.3390/ijms140612023] [PMID: 23739680]
[140]
Chmielewska-Kassassir, M.; Sobierajska, K.; Ciszewski, W.M.; Bukowiecka-Matusiak, M.; Szczesna, D.; Burzynska-Pedziwiatr, I.; Wiczkowski, W.; Wagner, W.; Wozniak, L.A. Polyphenol extract from evening primrose (Oenothera paradoxa) inhibits invasion properties of human malignant pleural mesothelioma cells. Biomolecules, 2020, 10(11), E1574.
[http://dx.doi.org/10.3390/biom10111574] [PMID: 33228230]
[141]
Kaewtunjai, N.; Wongpoomchai, R.; Imsumran, A.; Pompimon, W.; Athipornchai, A.; Suksamrarn, A.; Lee, T.R.; Tuntiwechapikul, W. Ginger extract promotes telomere shortening and cellular senescence in A549 lung cancer cells. ACS Omega, 2018, 3(12), 18572-18581.
[http://dx.doi.org/10.1021/acsomega.8b02853] [PMID: 32010796]
[142]
Udroiu, I.; Marinaccio, J.; Sgura, A. Epigallocatechin-3-gallate induces telomere shortening and clastogenic damage in glioblastoma cells. Environ. Mol. Mutagen., 2019, 60(8), 683-692.
[http://dx.doi.org/10.1002/em.22295] [PMID: 31026358]
[143]
Chimplee, S.; Graidist, P.; Srisawat, T.; Sukrong, S.; Bissanum, R.; Kanokwiroon, K. Anti-breast cancer potential of frullanolide from Grangea maderaspatana plant by inducing apoptosis. Oncol. Lett., 2019, 17(6), 5283-5291.
[http://dx.doi.org/10.3892/ol.2019.10209] [PMID: 31186745]
[144]
Kang, M.R.; Muller, M.T.; Chung, I.K. Telomeric DNA damage by topoisomerase I. A possible mechanism for cell killing by camptothecin. J. Biol. Chem., 2004, 279(13), 12535-12541.
[http://dx.doi.org/10.1074/jbc.M309779200] [PMID: 14729676]
[145]
Rowaiye, A.B.; Mendes, Y.J.T.; Olofinsae, S.A.; Oche, J.B.; Oladipo, O.H.; Okpalefe, O.A.; Ogidigo, J.O. Camptothecin shows better promise than curcumin in the inhibition of the human telomerase: A computational study. Heliyon, 2021, 7(8), e07742.
[http://dx.doi.org/10.1016/j.heliyon.2021.e07742] [PMID: 34485722]
[146]
Eboji, O.K.; Borges, G.; Harrington, L. Catechin from Burkea africana hook. Exhibits in vitro inhibition of human telomerase activity. Nat. Prod. Res., 2021, 35(24), 6175-79.
[PMID: 33930985]
[147]
Yang, C.S.; Wang, H.; Chen, J.X.; Zhang, J. Effects of tea catechins on cancer signaling pathways. Enzymes, 2014, 36, 195-221.
[http://dx.doi.org/10.1016/B978-0-12-802215-3.00010-0] [PMID: 27102705]
[148]
Yiannakopoulou, E.C. Targeting DNA methylation with green tea catechins. Pharmacology, 2015, 95(3-4), 111-116.
[http://dx.doi.org/10.1159/000375503] [PMID: 25792496]
[149]
Rahmati-Yamchi, M.; Ghareghomi, S.; Haddadchi, G.; Milani, M.; Aghazadeh, M.; Daroushnejad, H. Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line. Mol. Biol. Rep., 2014, 41(9), 6247-6252.
[http://dx.doi.org/10.1007/s11033-014-3505-y] [PMID: 24973886]
[150]
Luna-Dulcey, L.; Almada da Silva, J.; Jimenez-Renard, V.; Caleiras, E.; Mouron, S.; Quintela-Fandino, M.; Cominetti, M.R. [6]-Gingerol-derived semi-synthetic compound SSi6 inhibits tumor growth and metastatic dissemination in triple-negative breast cancer xenograft models. Cancers (Basel), 2021, 13(12), 2855.
[http://dx.doi.org/10.3390/cancers13122855] [PMID: 34201040]
[151]
Tuntiwechapikul, W.; Taka, T.; Songsomboon, C.; Kaewtunjai, N.; Imsumran, A.; Makonkawkeyoon, L.; Pompimon, W.; Lee, T.R. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells. J. Med. Food, 2010, 13(6), 1347-1354.
[http://dx.doi.org/10.1089/jmf.2010.1191] [PMID: 21091248]
[152]
Gharib, A.; Faezizadeh, Z. In vitro anti-telomerase activity of novel lycopene-loaded nanospheres in the human leukemia cell line K562. Pharmacogn. Mag., 2014, 10(37)(Suppl. 1), S157-S163.
[http://dx.doi.org/10.4103/0973-1296.127368] [PMID: 24914298]
[153]
Tao, A.; Wang, X.; Li, C. Effect of lycopene on oral squamous cell carcinoma cell growth by inhibiting IGF1 pathway. Cancer Manag. Res., 2021, 13, 723-732.
[http://dx.doi.org/10.2147/CMAR.S283927] [PMID: 33531840]
[154]
Long, C.; Xu, Q.B.; Ding, L.; Yang, L.; Ji, W.; Gao, F.; Ji, Y. Triptolide inhibits human telomerase reverse transcriptase by downregulating translation factors SP1 and c-Myc in Epstein-Barr virus-positive B lymphocytes. Oncol. Lett., 2021, 21(4), 280.
[http://dx.doi.org/10.3892/ol.2021.12541] [PMID: 33732356]
[155]
Zhang, Y.; Wang, H.; Liu, Y.; Wang, C.; Wang, J.; Long, C.; Guo, W.; Sun, X. Baicalein inhibits growth of Epstein-Barr virus-positive nasopharyngeal carcinoma by repressing the activity of EBNA1 Q-promoter. Biomed. Pharmacother., 2018, 102, 1003-1014.
[http://dx.doi.org/10.1016/j.biopha.2018.03.114] [PMID: 29710517]
[156]
Gao, Z.; Zhang, Y.; Zhou, H.; Lv, J. Baicalein inhibits the growth of oral squamous cell carcinoma cells by downregulating the expression of transcription factor Sp1. Int. J. Oncol., 2020, 56(1), 273-282.
[PMID: 31746368]
[157]
Liu, T.; Long, T.; Li, H. Curcumin suppresses the proliferation of oral squamous cell carcinoma through a specificity protein 1/nuclear factor-κB-dependent pathway. Exp. Ther. Med., 2021, 21(3), 202.
[http://dx.doi.org/10.3892/etm.2021.9635] [PMID: 33500696]
[158]
Moon, D.O.; Kim, M.O.; Choi, Y.H.; Lee, H.G.; Kim, N.D.; Kim, G.Y. Gossypol suppresses telomerase activity in human leukemia cells via regulating hTERT. FEBS Lett., 2008, 582(23-24), 3367-3373.
[http://dx.doi.org/10.1016/j.febslet.2008.08.029] [PMID: 18775705]
[159]
Jagadeesh, S.; Kyo, S.; Banerjee, P.P. Genistein represses telomerase activity via both transcriptional and posttranslational mechanisms in human prostate cancer cells. Cancer Res., 2006, 66(4), 2107-2115.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2494] [PMID: 16489011]
[160]
Javed, Z.; Khan, K.; Herrera-Bravo, J.; Naeem, S.; Iqbal, M.J.; Sadia, H.; Qadri, Q.R.; Raza, S.; Irshad, A.; Akbar, A.; Reiner, Ž.; Al-Harrasi, A.; Al-Rawahi, A.; Satmbekova, D.; Butnariu, M.; Bagiu, I.C.; Bagiu, R.V.; Sharifi-Rad, J. Genistein as a regulator of signaling pathways and microRNAs in different types of cancers. Cancer Cell Int., 2021, 21(1), 388.
[http://dx.doi.org/10.1186/s12935-021-02091-8] [PMID: 34289845]
[161]
Vucenik, I.; Druzijanic, A.; Druzijanic, N. Inositol hexaphosphate (IP6) and colon cancer: From concepts and first experiments to clinical application. Molecules, 2020, 25(24), 5931.
[http://dx.doi.org/10.3390/molecules25245931] [PMID: 33333775]
[162]
Kedhari Sundaram, M.; Raina, R.; Afroze, N.; Bajbouj, K.; Hamad, M.; Haque, S.; Hussain, A. Quercetin modulates signaling pathways and induces apoptosis in cervical cancer cells. Biosci. Rep., 2019, 39(8), BSR20190720.
[http://dx.doi.org/10.1042/BSR20190720] [PMID: 31366565]
[163]
Vafadar, A.; Shabaninejad, Z.; Movahedpour, A.; Fallahi, F.; Taghavipour, M.; Ghasemi, Y.; Akbari, M.; Shafiee, A.; Hajighadimi, S.; Moradizarmehri, S.; Razi, E.; Savardashtaki, A.; Mirzaei, H. Quercetin and cancer: New insights into its therapeutic effects on ovarian cancer cells. Cell Biosci., 2020, 10(1), 32.
[http://dx.doi.org/10.1186/s13578-020-00397-0] [PMID: 32175075]
[164]
Choi, Y.S.; Han, J.M.; Kang, Y.J.; Jung, H.J. Chloroform extract of Citrus unshiu markovich peel induces apoptosis and inhibits stemness in HeLa human cervical cancer cells. Mol. Med. Rep., 2021, 23(1), 86.
[http://dx.doi.org/10.3892/mmr.2020.11727] [PMID: 33236129]
[165]
Eliza, J.; Daisy, P.; Ignacimuthu, S. Antioxidant activity of costunolide and eremanthin isolated from Costus speciosus (Koen ex. Retz). Sm. Chem. Biol. Interact., 2010, 188(3), 467-472.
[http://dx.doi.org/10.1016/j.cbi.2010.08.002] [PMID: 20709041]
[166]
Liu, T.; Zhao, X.; Song, D.; Liu, Y.; Kong, W. Anticancer activity of Eremanthin against the human cervical cancer cells is due to G2/M phase cell cycle arrest, ROS-mediated necrosis-like cell death and inhibition of PI3K/AKT signalling pathway. J. BUON, 2020, 25(3), 1547-1553.
[PMID: 32862603]
[167]
Wu, J.; Wang, N.; Jin, G.; Xue, L. Tormentic acid induces anticancer effects in cisplatin-resistant human cervical cancer cells mediated via cell cycle arrest, ROS production, and targeting mTOR/PI3K/AKT signalling pathway. J. BUON, 2020, 25(1), 74-79.
[PMID: 32277616]
[168]
Zhang, J.; Feng, M.; Guan, W. Naturally occurring Aesculetin coumarin exerts antiproliferative effects in gastric cancer cells mediated via apoptotic cell death, cell cycle arrest and targeting PI3K/AKT/M-TOR signalling pathway. Acta Biochim. Pol., 2021, 68(1), 109-113.
[http://dx.doi.org/10.18388/abp.2020_5463] [PMID: 33728889]
[169]
Peng, X.; Ruan, C.; Lei, C.; He, A.; Wang, X.; Luo, R.; Cai, Y.; Dong, W.; Lin, J. Anticancer effects of Lanostane against human gastric cancer cells involves autophagy, apoptosis and modulation of m-TOR/PI3K/AKT signalling pathway. J. BUON, 2020, 25(3), 1463-1468.
[PMID: 32862591]
[170]
Yang, J.; Xiao, P.; Sun, J.; Guo, L. Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway. J. BUON, 2018, 23(1), 218-223.
[PMID: 29552787]
[171]
Wang, W-D.; Liu, Y.; Su, Y.; Xiong, X.Z.; Shang, D.; Xu, J.J.; Liu, H.J. Antitumor and apoptotic effects of cucurbitacin a in A-549 lung carcinoma cells is mediated via G2/M cell cycle arrest and M-TOR/PI3K/AKT signalling pathway. Afr. J. Tradit. Complement. Altern. Med., 2017, 14(2), 75-82.
[http://dx.doi.org/10.21010/ajtcam.v14i2.9] [PMID: 28573224]
[172]
Li, F.; Jiang, T.; Li, Q.; Ling, X. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: Did we miss something in CPT analogue molecular targets for treating human disease such as cancer? Am. J. Cancer Res., 2017, 7(12), 2350-2394.
[PMID: 29312794]
[173]
Garcia-Oliveira, P.; Otero, P.; Pereira, A.G.; Chamorro, F.; Carpena, M.; Echave, J.; Fraga-Corral, M.; Simal-Gandara, J.; Prieto, M.A. Status and challenges of plant-anticancer compounds in cancer treatment. Pharmaceuticals (Basel), 2021, 14(2), 157.
[http://dx.doi.org/10.3390/ph14020157] [PMID: 33673021]
[174]
Lyman, G.H.; Abella, E.; Pettengell, R. Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review. Crit. Rev. Oncol. Hematol., 2014, 90(3), 190-199.
[http://dx.doi.org/10.1016/j.critrevonc.2013.12.006] [PMID: 24434034]
[175]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[176]
Lee, W.L.; Huang, J.Y.; Shyur, L.F. Phytoagents for cancer management: Regulation of nucleic acid oxidation, ROS, and related mechanisms. Oxid. Med. Cell. Longev., 2013, 2013, 925804.
[http://dx.doi.org/10.1155/2013/925804] [PMID: 24454991]
[177]
Choudhari, A.S.; Mandave, P.C.; Deshpande, M.; Ranjekar, P.; Prakash, O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front. Pharmacol., 2020, 10, 1614.
[http://dx.doi.org/10.3389/fphar.2019.01614] [PMID: 32116665]
[178]
Youn, D.H.; Park, J.; Kim, H.L.; Jung, Y.; Kang, J.; Lim, S.; Song, G.; Kwak, H.J.; Um, J.Y. Berberine improves benign prostatic hyperplasia via suppression of 5 alpha reductase and extracellular signal-regulated kinase in vivo and in vitro. Front. Pharmacol., 2018, 9, 773.
[http://dx.doi.org/10.3389/fphar.2018.00773] [PMID: 30061836]
[179]
Mahata, S.; Bharti, A.C.; Shukla, S.; Tyagi, A.; Husain, S.A.; Das, B.C. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. Mol. Cancer, 2011, 10(1), 39.
[http://dx.doi.org/10.1186/1476-4598-10-39] [PMID: 21496227]
[180]
Cojocneanu Petric, R.; Braicu, C.; Raduly, L.; Zanoaga, O.; Dragos, N.; Monroig, P.; Dumitrascu, D.; Berindan-Neagoe, I. Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. OncoTargets Ther., 2015, 8, 2053-2066.
[http://dx.doi.org/10.2147/OTT.S83597] [PMID: 26273208]
[181]
Chen, H.; Zhu, B.; Zhao, L.; Liu, Y.; Zhao, F.; Feng, J.; Jin, Y.; Sun, J.; Geng, R.; Wei, Y. Allicin inhibits proliferation and invasion in vitro and in vivo via SHP-1-Mediated STAT3 signaling in cholangiocarcinoma. Cell. Physiol. Biochem., 2018, 47(2), 641-653.
[http://dx.doi.org/10.1159/000490019] [PMID: 29794468]
[182]
Wu, W.; Tang, S.N.; Zhang, Y.; Puppala, M.; Cooper, T.K.; Xing, C.; Jiang, C.; Lü, J. Prostate cancer xenograft inhibitory activity and pharmacokinetics of decursinol, a metabolite of angelica gigas pyranocoumarins, in mouse models. Am. J. Chin. Med., 2017, 45(8), 1773-1792.
[http://dx.doi.org/10.1142/S0192415X17500963] [PMID: 29121805]
[183]
Chimento, A.; Santarsiero, A.; Iacopetta, D.; Ceramella, J.; De Luca, A.; Infantino, V.; Parisi, O.I.; Avena, P.; Bonomo, M.G.; Saturnino, C.; Sinicropi, M.S.; Pezzi, V. A phenylacetamide resveratrol derivative exerts inhibitory effects on breast cancer cell growth. Int. J. Mol. Sci., 2021, 22(10), 5255.
[http://dx.doi.org/10.3390/ijms22105255] [PMID: 34067547]
[184]
Li, Q.; Xu, D.; Gu, Z.; Li, T.; Huang, P.; Ren, L. Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA-129-1-3p-mediated calcium signaling pathway. J. Biochem. Mol. Toxicol., 2021, 35(7), e22794.
[http://dx.doi.org/10.1002/jbt.22794] [PMID: 33913213]
[185]
Fasoulakis, Z.; Koutras, A.; Syllaios, A.; Schizas, D.; Garmpis, N.; Diakosavvas, M.; Angelou, K.; Tsatsaris, G.; Pagkalos, A.; Ntounis, T.; Kontomanolis, E.N. Breast cancer apoptosis and the therapeutic role of luteolin. Chirurgia (Bucur.), 2021, 116(2), 170-177.
[http://dx.doi.org/10.21614/chirurgia.116.2.170] [PMID: 33950812]
[186]
Wu, H.T.; Liu, Y.E.; Hsu, K.W.; Wang, Y.F.; Chan, Y.C.; Chen, Y.; Chen, D.R. MLL3 Induced by luteolin causes apoptosis in tamoxifen-resistant breast cancer cells through H3K4 monomethylation and suppression of the PI3K/AKT/mTOR Pathway. Am. J. Chin. Med., 2020, 48(5), 1221-1241.
[http://dx.doi.org/10.1142/S0192415X20500603] [PMID: 32668964]
[187]
Pessoa, C.; Silveira, E.R.; Lemos, T.L.; Wetmore, L.A.; Moraes, M.O.; Leyva, A. Antiproliferative effects of compounds derived from plants of Northeast Brazil. Phytother. Res., 2000, 14(3), 187-191.
[http://dx.doi.org/10.1002/(SICI)1099-1573(200005)14:3<187::AID-PTR572>3.0.CO;2-I] [PMID: 10815012]
[188]
Ahmed, E.Y.; Elserwy, W.S.; El-Mansy, M.F.; Serry, A.M.; Salem, A.M.; Abdou, A.M.; Abdelrahman, B.A.; Elsayed, K.H.; Abd Elaziz, M.R. Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives. Bioorg. Med. Chem. Lett., 2021, 48, 128258.
[http://dx.doi.org/10.1016/j.bmcl.2021.128258] [PMID: 34246754]
[189]
Kustiati, U.; Ratih, T.S.D.; Agung, N.D.A.; Kusindarta, D.L.; Wihadmadyatami, H. In silico molecular docking and in vitro analysis of ethanolic extract Ocimum sanctum Linn.: Inhibitory and apoptotic effects against non-small cell lung cancer. Vet. World, 2021, 14(12), 3175-3187.
[http://dx.doi.org/10.14202/vetworld.2021.3175-3187] [PMID: 35153410]
[190]
Zhao, Y.N.; Cao, Y.N.; Sun, J.; Liang, Z.; Wu, Q.; Cui, S.H.; Zhi, D.F.; Guo, S.T.; Zhen, Y.H.; Zhang, S.B. Anti-breast cancer activity of resveratrol encapsulated in liposomes. J. Mater. Chem. B Mater. Biol. Med., 2020, 8(1), 27-37.
[http://dx.doi.org/10.1039/C9TB02051A] [PMID: 31746932]
[191]
Caldas, M.; Santos, A.C.; Veiga, F.; Rebelo, R.; Reis, R.L.; Correlo, V.M. Melanin nanoparticles as a promising tool for biomedical applications - a review. Acta Biomater., 2020, 105, 26-43.
[http://dx.doi.org/10.1016/j.actbio.2020.01.044] [PMID: 32014585]
[192]
Liu, H.; Yang, Y.; Liu, Y.; Pan, J.; Wang, J.; Man, F.; Zhang, W.; Liu, G. Melanin-like nanomaterials for advanced biomedical applications: A versatile platform with extraordinary promise. Adv. Sci. (Weinh.), 2020, 7(7), 1903129.
[http://dx.doi.org/10.1002/advs.201903129] [PMID: 32274309]

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