Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Nimbolide, a Neem Limonoid, Inhibits Angiogenesis in Breast Cancer by Abrogating Aldose Reductase Mediated IGF-1/PI3K/Akt Signalling

Author(s): Ramesh Nivetha, Soundararajan Arvindh, Abdul Basit Baba, Deepak Reddy Gade, Gopisetty Gopal, Chitrathara K, Kallamadi Prathap Reddy, G. Bhanuprakash Reddy and Siddavaram Nagini*

Volume 22, Issue 14, 2022

Published on: 29 April, 2022

Page: [2619 - 2636] Pages: 18

DOI: 10.2174/1871520622666220204115151

Price: $65

Abstract

Background & Objective: The insulin/IGF-1R/PI3K/Akt signalling cascade is increasingly being linked to breast cancer development, with aldose reductase (AR) playing a key role in mediating the crosstalk between this pathway and angiogenesis. The current study was designed to investigate whether nimbolide, a neem limonoid, targets the oncogenic signaling network to prevent angiogenesis in breast cancer.

Methods: Breast cancer cells (MCF-7, MDA-MB-231), EAhy926 endothelial cells, MDA-MB-231 xenografted nude mice, and tumour tissues from breast cancer patients were used for the study. The expression of AR and key players in IGF-1/PI3K/Akt signaling and angiogenesis was evaluated by qRT-PCR, immunoblotting, and immunohistochemistry. Molecular docking and simulation, overexpression, and knockdown experiments were performed to determine whether nimbolide targets AR and IGF-1R.

Results: Nimbolide inhibited AR with consequent blockade of the IGF-1/PI3K/Akt and /HIF-1alpha/VEGF signalling circuit by influencing the phosphorylation and intracellular localisation of key signaling molecules. The downregulation of DNMT-1, HDAC-6, miR-21, HOTAIR, and H19 with the upregulation of miR-148a/miR-152 indicated that nimbolide regulates AR and IGF-1/PI3K/Akt signaling via epigenetic modifications. Coadministration of nimbolide with metformin and the chemotherapeutic drugs tamoxifen/cisplatin displayed higher efficacy than single agents in inhibiting IGF-1/PI3K/Akt/AR signaling. Grade-wise increases in IGF-1R and AR expression in breast cancer tissues underscore their value as biomarkers of progression.

Conclusion: This study provides evidence for the anticancer effects of nimbolide in cellular and mouse models of breast cancer besides providing leads for new drug combinations. It has also opened up avenues for investigating potential molecules such as AR for therapeutic targeting of cancer.

Keywords: Aldose reductase, angiogenesis, breast cancer, IGF-1, nimbolide, PI3K/Akt.

« Previous Next »
Graphical Abstract

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN esti-mates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Nagini, S. Breast cancer: Current molecular therapeutic targets and new players. Anticancer. Agents Med. Chem., 2017, 17(2), 152-163.
[http://dx.doi.org/10.2174/1871520616666160502122724] [PMID: 27137076]
[3]
Feng, Y.; Spezia, M.; Huang, S.; Yuan, C.; Zeng, Z.; Zhang, L.; Ji, X.; Liu, W.; Huang, B.; Luo, W.; Liu, B.; Lei, Y.; Du, S.; Vuppalapati, A.; Luu, H.H.; Haydon, R.C.; He, T.C.; Ren, G. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis., 2018, 5(2), 77-106.
[http://dx.doi.org/10.1016/j.gendis.2018.05.001] [PMID: 30258937]
[4]
Christopoulos, P.F.; Corthay, A.; Koutsilieris, M. Aiming for the insulin-like growth factor-1 system in breast cancer therapeutics. Cancer Treat. Rev., 2018, 63, 79-95.
[http://dx.doi.org/10.1016/j.ctrv.2017.11.010] [PMID: 29253837]
[5]
Lero, M.W.; Shaw, L.M. Diversity of insulin and IGF signaling in breast cancer: Implications for therapy. Mol. Cell. Endocrinol., 2021, 527, 111213.
[http://dx.doi.org/10.1016/j.mce.2021.111213] [PMID: 33607269]
[6]
Farabaugh, S.M.; Litzenburger, B.C.; Elangovan, A.; Pecar, G.; Walheim, L.; Atkinson, J.M.; Lee, A.V. IGF1R constitutive activation ex-pands luminal progenitors and influences lineage differentiation during breast tumorigenesis. Dev. Biol., 2020, 463(1), 77-87.
[http://dx.doi.org/10.1016/j.ydbio.2020.04.007] [PMID: 32376245]
[7]
Cevenini, A.; Orrù, S.; Mancini, A.; Alfieri, A.; Buono, P.; Imperlini, E. Molecular signatures of the insulin-like growth factor 1-mediated epithelial-mesenchymal transition in breast, lung and gastric cancers. Int. J. Mol. Sci., 2018, 19(8), 2411.
[http://dx.doi.org/10.3390/ijms19082411] [PMID: 30111747]
[8]
De Francesco, E.M.; Sims, A.H.; Maggiolini, M.; Sotgia, F.; Lisanti, M.P.; Clarke, R.B. GPER mediates the angiocrine actions induced by IGF1 through the HIF-1/VEGF pathway in the breast tumor microenvironment. Breast Cancer Res., 2017, 19(1), 129.
[http://dx.doi.org/10.1186/s13058-017-0923-5] [PMID: 29212519]
[9]
Tammali, R.; Reddy, A.B.; Srivastava, S.K.; Ramana, K.V. Inhibition of aldose reductase prevents angiogenesis in vitro and in vivo. Angiogenesis, 2011, 14(2), 209-221.
[http://dx.doi.org/10.1007/s10456-011-9206-4] [PMID: 21409599]
[10]
Abdillahi, M.; Ananthakrishnan, R.; Vedantham, S.; Shang, L.; Zhu, Z.; Rosario, R.; Zirpoli, H.; Bohren, K.M.; Gabbay, K.H.; Ramasamy, R. Aldose reductase modulates cardiac glycogen synthase kinase-3 phosphorylation during ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol., 2012, 303(3), H297-H308.
[http://dx.doi.org/10.1152/ajpheart.00999.2011] [PMID: 22661511]
[11]
Khayami, R.; Hashemi, S.R.; Kerachian, M.A. Role of aldo-keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential. J. Cell. Mol. Med., 2020, 24(16), 8890-8902.
[http://dx.doi.org/10.1111/jcmm.15581] [PMID: 32633024]
[12]
Sonowal, H.; Ramana, K.V. Development of aldose reductase inhibitors for the treatment of inflammatory disorders and cancer: Current drug design strategies and future directions. Curr. Med. Chem., 2021, 28(19), 3683-3712.
[http://dx.doi.org/10.2174/0929867327666201027152737] [PMID: 33109031]
[13]
Reddy, K.A.; Kumar, P.U.; Srinivasulu, M.; Triveni, B.; Sharada, K.; Ismail, A.; Reddy, G.B. Overexpression and enhanced specific activi-ty of aldoketo reductases (AKR1B1 & AKR1B10) in human breast cancers. Breast, 2017, 31, 137-143.
[http://dx.doi.org/10.1016/j.breast.2016.11.003] [PMID: 27855345]
[14]
Han, C.; Gao, L.; Zhao, L.; Sheng, Q.; Zhang, C.; An, Z.; Xia, T.; Ding, Y.; Wang, J.; Bai, H.; Dou, X.; An Xia, T.; Ding, Y.; Wang, J.; Bai, H.; Dou, X. Immunohistochemistry detects increased expression of aldo-keto reductase family 1 member B10 (AKR1B10) in early-stage hepatocellular carcinoma. Med. Sci. Monit., 2018, 24, 7414-7423.
[http://dx.doi.org/10.12659/MSM.910738] [PMID: 30328412]
[15]
Fang, C.Y.; Lin, Y.H.; Chen, C.L. Overexpression of AKR1B10 predicts tumor recurrence and short survival in oral squamous cell carci-noma patients. J. Oral Pathol. Med., 2019, 48(8), 712-719.
[http://dx.doi.org/10.1111/jop.12891] [PMID: 31237374]
[16]
Demirkol Canl S.; Seza, E.G.; Sheraj, I.; Gömçeli, I.; Turhan, N.; Carberry, S.; Prehn, J.H.M.; Güre, A.O.; Banerjee, S. Evaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathway. Carcinogenesis, 2020, 41(9), 1219-1228.
[http://dx.doi.org/10.1093/carcin/bgaa072] [PMID: 32628753]
[17]
Liu, Z.; Yan, R.; Al-Salman, A.; Shen, Y.; Bu, Y.; Ma, J.; Luo, D.X.; Huang, C.; Jiang, Y.; Wilber, A.; Mo, Y.Y.; Huang, M.C.; Zhao, Y.; Cao, D. Epidermal growth factor induces tumour marker AKR1B10 expression through activator protein-1 signalling in hepatocellular car-cinoma cells. Biochem. J., 2012, 442(2), 273-282.
[http://dx.doi.org/10.1042/BJ20111322] [PMID: 22329800]
[18]
Wu, X.; Li, X.; Fu, Q.; Cao, Q.; Chen, X.; Wang, M.; Yu, J.; Long, J.; Yao, J.; Liu, H.; Wang, D.; Liao, R.; Dong, C. AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program. J. Exp. Med., 2017, 214(4), 1065-1079.
[http://dx.doi.org/10.1084/jem.20160903] [PMID: 28270406]
[19]
Geng, N.; Jin, Y.; Li, Y.; Zhu, S.; Bai, H. AKR1B10 inhibitor epalrestat facilitates sorafenib-induced apoptosis and autophagy via targeting the mTOR pathway in hepatocellular carcinoma. Int. J. Med. Sci., 2020, 17(9), 1246-1256.
[http://dx.doi.org/10.7150/ijms.42956] [PMID: 32547320]
[20]
Ji, J.; Xu, M.X.; Qian, T.Y.; Zhu, S.Z.; Jiang, F.; Liu, Z.X.; Xu, W.S.; Zhou, J.; Xiao, M.B. The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer. Mol. Biol. Rep., 2020, 47(8), 6091-6103.
[http://dx.doi.org/10.1007/s11033-020-05685-z] [PMID: 32761301]
[21]
Abo-Elmatty, D.M.; Ahmed, E.A.; Tawfik, M.K.; Helmy, S.A. Metformin enhancing the antitumor efficacy of carboplatin against Ehrlich solid carcinoma grown in diabetic mice: Effect on IGF-1 and tumoral expression of IGF-1 receptors. Int. Immunopharmacol., 2017, 44, 72-86.
[http://dx.doi.org/10.1016/j.intimp.2017.01.002] [PMID: 28088698]
[22]
Samuel, S.M.; Varghese, E.; Kubatka, P.; Triggle, C.R.; Büsselberg, D. Metformin: the answer to cancer in a flower? Current knowledge and future prospects of metformin as an anti-cancer agent in breast cancer. Biomolecules, 2019, 9(12), 846.
[http://dx.doi.org/10.3390/biom9120846] [PMID: 31835318]
[23]
Biello, F.; Platini, F.; D’Avanzo, F.; Cattrini, C.; Mennitto, A.; Genestroni, S.; Martini, V.; Marzullo, P.; Aimaretti, G.; Gennari, A.; Mar-zullo, P.; Aimaretti, G.; Gennari, A. Insulin/IGF axis in breast cancer: Clinical evidence and translational insights. Biomolecules, 2021, 11(1), 125.
[http://dx.doi.org/10.3390/biom11010125] [PMID: 33477996]
[24]
Leng, W.; Jiang, J.; Chen, B.; Wu, Q. Metformin and malignant tumors: Not over the hill. Diabetes Metab. Syndr. Obes., 2021, 14, 3673-3689.
[http://dx.doi.org/10.2147/DMSO.S326378] [PMID: 34429626]
[25]
Huang, L.; He, R.; Luo, W.; Zhu, Y.S.; Li, J.; Tan, T.; Zhang, X.; Hu, Z.; Luo, D. Aldo-keto reductase family 1 member B10 inhibitors: potential drugs for cancer treatment. Recent Patents Anticancer Drug Discov., 2016, 11(2), 184-196.
[http://dx.doi.org/10.2174/1574892811888160304113346] [PMID: 26844556]
[26]
Kishore, T.K.K.; Ganugula, R.; Gade, D.R.; Reddy, G.B.; Nagini, S. Gedunin abrogates aldose reductase, PI3K/Akt/mToR, and NF-B signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis. Tumour Biol., 2016, 37(2), 2083-2093.
[http://dx.doi.org/10.1007/s13277-015-4003-0] [PMID: 26342697]
[27]
Tanagala, K.K.K.; Baba, A.B.; Kowshik, J.; Reddy, G.B.; Nagini, S. Gedunin, a neem limonoid in combination with epalrestat inhibits can-cer hallmarks by attenuating aldose reductase-driven oncogenic signaling in SCC131 oral cancer cells. Anticancer. Agents Med. Chem., 2018, 18(14), 2042-2052.
[http://dx.doi.org/10.2174/1871520618666180731093433] [PMID: 30062975]
[28]
Nagini, S.; Vidya Priyadarsini, R. Apoptosis induction by nimbolide, a limonoid from Azadirachta indica: Molecular targets and signaling networks.Novel apoptotic regulators in carcinogenesis; Chen, G.C; Lai, P.B.S., Ed.; Springer Verlag, 2012, pp. 27-44.
[29]
Nagini, S.; Nivetha, R.; Palrasu, M.; Mishra, R. Nimbolide, a neem limonoid, is a promising candidate for the anticancer drug arsenal. J. Med. Chem., 2021, 64(7), 3560-3577.
[http://dx.doi.org/10.1021/acs.jmedchem.0c02239] [PMID: 33739088]
[30]
Wang, L.; Phan, D.D.; Zhang, J.; Ong, P.S.; Thuya, W.L.; Soo, R.; Wong, A.L.; Yong, W.P.; Lee, S.C.; Ho, P.C.; Sethi, G.; Goh, B.C. Anti-cancer properties of nimbolide and pharmacokinetic considerations to accelerate its development. Oncotarget, 2016, 7(28), 44790-44802.
[http://dx.doi.org/10.18632/oncotarget.8316] [PMID: 27027349]
[31]
Priyadarsini, R.V.; Manikandan, P.; Kumar, G.H.; Nagini, S. The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radic. Res., 2009, 43(5), 492-504.
[http://dx.doi.org/10.1080/10715760902870637] [PMID: 19391054]
[32]
Harish Kumar, G.; Vidya Priyadarsini, R.; Vinothini, G.; Vidjaya Letchoumy, P.; Nagini, S. The neem limonoids azadirachtin and nimbo-lide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis. Invest. New Drugs, 2010, 28(4), 392-401.
[http://dx.doi.org/10.1007/s10637-009-9263-3] [PMID: 19458912]
[33]
Kavitha, K.; Vidya Priyadarsini, R.; Anitha, P.; Ramalingam, K.; Sakthivel, R.; Purushothaman, G.; Singh, A.K.; Karunagaran, D.; Nagini, S. Nimbolide, a neem limonoid abrogates canonical NF-B and Wnt signaling to induce caspase-dependent apoptosis in human hepatocar-cinoma (HepG2) cells. Eur. J. Pharmacol., 2012, 681(1-3), 6-14.
[http://dx.doi.org/10.1016/j.ejphar.2012.01.024] [PMID: 22327045]
[34]
Sophia, J.; Kiran Kishore, T. K.; Kowshik, J.; Mishra, R.; Nagini, S. Nimbolide, a neem limonoid inhibits Phosphatidyl Inositol-3 Kinase to activate Glycogen Synthase Kinase-3β in a hamster model of oral oncogenesis. Sci. Rep., 2016, 6, 22192.
[http://dx.doi.org/10.1038/srep22192] [PMID: 26902162]
[35]
Sophia, J.; Kowshik, J.; Dwivedi, A.; Bhutia, S.K.; Manavathi, B.; Mishra, R.; Nagini, S. Nimbolide, a neem limonoid inhibits cytoprotec-tive autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3 signalling pathway in oral cancer. Cell Death Dis., 2018, 9(11), 1087.
[http://dx.doi.org/10.1038/s41419-018-1126-4] [PMID: 30352996]
[36]
Kowshik, J.; Mishra, R.; Sophia, J.; Rautray, S.; Anbarasu, K.; Reddy, G.D.; Dixit, M.; Mahalingam, S.; Nagini, S. Nimbolide upregulates RECK by targeting miR-21 and HIF-1 in cell lines and in a hamster oral carcinogenesis model. Sci. Rep., 2017, 7(1), 2045.
[http://dx.doi.org/10.1038/s41598-017-01960-5] [PMID: 28515436]
[37]
Elumalai, P.; Arunkumar, R.; Benson, C.S.; Sharmila, G.; Arunakaran, J. Nimbolide inhibits IGF-I-mediated PI3K/Akt and MAPK signal-ling in human breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem. Funct., 2014, 32(5), 476-484.
[http://dx.doi.org/10.1002/cbf.3040] [PMID: 24888707]
[38]
Jyothi Buggana, S.; Paturi, M.C.; Perka, H.; Gade, D.R.; Vvs, R.P. Novel 2,4-disubstituted quinazolines as cytotoxic agents and JAK2 in-hibitors: Synthesis, in vitro evaluation and molecular dynamics studies. Comput. Biol. Chem., 2019, 79, 110-118.
[http://dx.doi.org/10.1016/j.compbiolchem.2019.01.008] [PMID: 30785020]
[39]
Legrand-Poels, S.; Schoonbrodt, S.; Piette, J. Regulation of interleukin-6 gene expression by pro-inflammatory cytokines in a colon cancer cell line. Biochem. J., 2000, 349(Pt 3), 765-773.
[http://dx.doi.org/10.1042/bj3490765]
[40]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[41]
Saraswat, M.; Mrudula, T.; Kumar, P.U.; Suneetha, A.; Rao, Rao T.S.; Srinivasulu, M.; Reddy, B. Overexpression of aldose reductase in human cancer tissues. Med. Sci. Monit., 2006, 12(12), CR525-CR529.
[PMID: 17136009]
[42]
Odeh, L.H.; Talib, W.H.; Basheti, I.A. Synergistic effect of thymoquinone and melatonin against breast cancer implanted in mice. J. Cancer Res. Ther., 2018, 14(Suppl.), S324-S330.
[http://dx.doi.org/10.4103/0973-1482.235349] [PMID: 29970684]
[43]
Xia, C.; Chen, R.; Chen, J.; Qi, Q.; Pan, Y.; Du, L.; Xiao, G.; Jiang, S. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice. Sci. Rep., 2017, 7, 43373.
[http://dx.doi.org/10.1038/srep43373] [PMID: 28252027]
[44]
De, A.; Kuppusamy, G. Metformin in breast cancer: preclinical and clinical evidence. Curr. Probl. Cancer, 2020, 44(1), 100488.
[http://dx.doi.org/10.1016/j.currproblcancer.2019.06.003] [PMID: 31235186]
[45]
Wang, J.; Li, G.; Wang, Y.; Tang, S.; Sun, X.; Feng, X.; Li, Y.; Bao, G.; Li, P.; Mao, X.; Wang, M.; Liu, P. Suppression of tumor angiogen-esis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1α/VEGF secretion axis. Oncotarget, 2015, 6(42), 44579-44592.
[http://dx.doi.org/10.18632/oncotarget.6373] [PMID: 26625311]
[46]
Wang, J.C.; Li, G.Y.; Li, P.P.; Sun, X.; Li, W.M.; Li, Y.; Lu, S.Y.; Liu, P.J. Suppression of hypoxia-induced excessive angiogenesis by metformin via elevating tumor blood perfusion. Oncotarget, 2017, 8(43), 73892-73904.
[http://dx.doi.org/10.18632/oncotarget.18029] [PMID: 29088755]
[47]
Farahi, A.; Abedini, M.R.; Javdani, H.; Arzi, L.; Chamani, E.; Farhoudi, R.; Talebloo, N.; Hoshyar, R. Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies. Mol. Cell. Biochem., 2021, 476(9), 3341-3351.
[http://dx.doi.org/10.1007/s11010-020-04043-8] [PMID: 33929675]
[48]
Xue, L.; Chen, F.; Yue, F.; Camacho, L.; Kothapalli, S.; Wei, G.; Huang, S.; Mo, Q.; Ma, F.; Li, Y.; Jiralerspong, S. Metformin and an insu-lin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer. Breast Cancer Res. Treat., 2021, 185(1), 73-84.
[http://dx.doi.org/10.1007/s10549-020-05927-5] [PMID: 32940848]
[49]
Pooladanda, V.; Bandi, S.; Mondi, S.R.; Gottumukkala, K.M.; Godugu, C. Nimbolide epigenetically regulates autophagy and apoptosis in breast cancer. Toxicol. In Vitro, 2018, 51, 114-128.
[http://dx.doi.org/10.1016/j.tiv.2018.05.010] [PMID: 29778718]
[50]
Arumugam, A.; Subramani, R.; Lakshmanaswamy, R. Involvement of actin cytoskeletal modifications in the inhibition of triple-negative breast cancer growth and metastasis by nimbolide. Mol. Ther. Oncolytics, 2021, 20, 596-606.
[http://dx.doi.org/10.1016/j.omto.2021.02.014] [PMID: 33768141]
[51]
Sehgal, P.; Kumar, N.; Praveen Kumar, V.R.; Patil, S.; Bhattacharya, A.; Vijaya Kumar, M.; Mukherjee, G.; Kondaiah, P. Regulation of protumorigenic pathways by insulin like growth factor binding protein2 and its association along with β-catenin in breast cancer lymph node metastasis. Mol. Cancer, 2013, 12(1), 63.
[http://dx.doi.org/10.1186/1476-4598-12-63] [PMID: 23767917]
[52]
Karkare, S.; Chhipa, R.R.; Anderson, J.; Liu, X.; Henry, H.; Gasilina, A.; Nassar, N.; Ghosh, J.; Clark, J.P.; Kumar, A.; Pauletti, G.M.; Ghosh, P.K.; Dasgupta, B. Direct inhibition of retinoblastoma phosphorylation by nimbolide causes cell-cycle arrest and suppresses glio-blastoma growth. Clin. Cancer Res., 2014, 20(1), 199-212.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0762] [PMID: 24170547]
[53]
Liu, J-F.; Hou, C-H.; Lin, F-L.; Tsao, Y-T.; Hou, S-M. Nimbolide induces ROS-regulated apoptosis and inhibits cell migration in osteosar-coma. Int. J. Mol. Sci., 2015, 16(10), 23405-23424.
[http://dx.doi.org/10.3390/ijms161023405] [PMID: 26426012]
[54]
Subramani, R.; Gonzalez, E.; Arumugam, A.; Nandy, S.; Gonzalez, V.; Medel, J.; Camacho, F.; Ortega, A.; Bonkoungou, S.; Narayan, M.; Dwivedi, Ak.; Lakshmanaswamy, R. Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and in-hibition of epithelial-to-mesenchymal transition. Sci. Rep., 2016, 6, 19819.
[http://dx.doi.org/10.1038/srep19819] [PMID: 26804739]
[55]
Bid, H.K.; Zhan, J.; Phelps, D.A.; Kurmasheva, R.T.; Houghton, P.J. Potent inhibition of angiogenesis by the IGF-1 receptor-targeting anti-body SCH717454 is reversed by IGF-2. Mol. Cancer Ther., 2012, 11(3), 649-659.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0575] [PMID: 22188815]
[56]
Gennari, A.; Foca, F.; Zamarchi, R.; Rocca, A.; Amadori, D.; De Censi, A.; Bologna, A.; Cavanna, L.; Gianni, L.; Scaltriti, L.; Rossi, E.; Facchinetti, A.; Martini, V.; Bruzzi, P.; Nanni, O. Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial. Breast Cancer Res. Treat., 2020, 181(1), 61-68.
[http://dx.doi.org/10.1007/s10549-020-05596-4] [PMID: 32200486]
[57]
Saxena, A.; Tammali, R.; Ramana, K.V.; Srivastava, S.K. Aldose reductase inhibition prevents colon cancer growth by restoring phospha-tase and tensin homolog through modulation of miR-21 and FOXO3a. Antioxid. Redox Signal., 2013, 18(11), 1249-1262.
[http://dx.doi.org/10.1089/ars.2012.4643] [PMID: 22978663]
[58]
Xu, Q.; Jiang, Y.; Yin, Y.; Li, Q.; He, J.; Jing, Y.; Qi, Y.T.; Xu, Q.; Li, W.; Lu, B.; Peiper, S.S.; Jiang, B.H.; Liu, L.Z. A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1. J. Mol. Cell Biol., 2013, 5(1), 3-13.
[http://dx.doi.org/10.1093/jmcb/mjs049] [PMID: 22935141]
[59]
Wen, Y.Y.; Liu, W.T.; Sun, H.R.; Ge, X.; Shi, Z.M.; Wang, M.; Li, W.; Zhang, J.Y.; Liu, L.Z.; Jiang, B.H. IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer. Sci. Rep., 2017, 7(1), 15897.
[http://dx.doi.org/10.1038/s41598-017-15607-y] [PMID: 29162853]
[60]
Cantile, M.; Di Bonito, M.; Cerrone, M.; Collina, F.; De Laurentiis, M.; Botti, G. Long non-coding RNA HOTAIR in breast cancer therapy. Cancers (Basel), 2020, 12(5), 1197.
[http://dx.doi.org/10.3390/cancers12051197] [PMID: 32397382]
[61]
Wong, K.K. DNMT1: A key drug target in triple-negative breast cancer. Semin. Cancer Biol., 2021, 72, 198-213.
[http://dx.doi.org/10.1016/j.semcancer.2020.05.010] [PMID: 32461152]
[62]
Yu, S.; Cai, X.; Wu, C.; Liu, Y.; Zhang, J.; Gong, X.; Wang, X.; Wu, X.; Zhu, T.; Mo, L.; Gu, J.; Yu, Z.; Chen, J.; Thiery, J.P.; Chai, R.; Chen, L. Targeting HSP90-HDAC6 regulating network implicates precision treatment of breast cancer. Int. J. Biol. Sci., 2017, 13(4), 505-517.
[http://dx.doi.org/10.7150/ijbs.18834] [PMID: 28529458]
[63]
Ekyalongo, R.C.; Yee, D. Revisiting the IGF-1R as a breast cancer target. NPJ Precis. Oncol., 2017, 1, 14.
[http://dx.doi.org/10.1038/s41698-017-0017-y] [PMID: 29152592]
[64]
Alam, M.; Kashyap, T.; Mishra, P.; Panda, A.K.; Nagini, S.; Mishra, R. Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance. Head Neck, 2019, 41(1), 185-197.
[PMID: 30549344]
[65]
Mahmoud, N.; Saeed, M.E.M.; Sugimoto, Y.; Klauck, S.M.; Greten, H.J.; Efferth, T. Cytotoxicity of nimbolide towards multidrug-resistant tumor cells and hypersensitivity via cellular metabolic modulation. Oncotarget, 2018, 9(87), 35762-35779.
[http://dx.doi.org/10.18632/oncotarget.26299] [PMID: 30515268]
[66]
Zhang, J.; Wang, N.; Li, Q.; Zhou, Y.; Luan, Y. A two-pronged photodynamic nanodrug to prevent metastasis of basal-like breast cancer. Chem. Commun. (Camb.), 2021, 57(18), 2305-2308.
[http://dx.doi.org/10.1039/D0CC08162K] [PMID: 33533351]

Rights & Permissions Print Cite
Article Metrics
27
1
© 2024 Bentham Science Publishers | Privacy Policy