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Anti-Cancer Agents in Medicinal Chemistry

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

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Research Article

Demethylzeylasteral Exerts Antitumor Effects via Disruptive Autophagic Flux and Apoptotic Cell Death in Human Colorectal Cancer Cells and Increases Cell Chemosensitivity to 5-Fluorouracil

Author(s): Guiyuan Liu, Dengxiang Lai, Yi Jiang, Hongjing Yang, Hui Zhao, Yonghui Zhang, Dan Liu and Yi Pang*

Volume 22, Issue 5, 2022

Published on: 08 June, 2021

Page: [851 - 863] Pages: 13

DOI: 10.2174/1871520621666210608104021

Price: $65

Abstract

Background: Demethylzeylasteral (ZST93), a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF), has been reported to exert antineoplastic effects in several cancer cell types. However, the anti-tumour effects of ZST93 in human colorectal cancer (CRC) cells are unknown.

Objective: The aim of the present study was to evaluate the antitumor effects of ZST93 on cell cycle arrest, disruptive autophagic flux, apoptotic cell death and enhanced chemosensitivity to 5-FU in human CRC cells.

Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, immunoblotting, immunofluorescence, 5-ethynyl-20-deoxyuridine (EdU) incorporation assay and autophagy analysis were used to evaluate the effects of ZST93 on cell viability, cell cycle progression, apoptosis and autophagy in two human CRC cell lines. Moreover, ZST93’s combined anti-tumour effects with 5-fluorouracil (5-FU) were evaluated.

Results: ZST93 inhibited CRC cell proliferation and growth. It was responsible for blocked cell cycle transition by arresting CRC cells in the G0/G1 phase via down-regulation of CDK4, CDK6, Cyclin D1 and c-MYC. Moreover, ZST93 induced suppressive autophagic flux and caspase-3-dependent cell death, which was further strengthened by the blocking of the autophagy process using chloroquine (CQ). Moreover, ZST93 enhanced CRC cells’ chemosensitivity to 5-FU via modulation of autophagy and apoptosis.

Conclusion: ZST93 exerts anti-tumor effects via disruptive autophagic flux and apoptotic cell death in human CRC cells and increases cell chemosensitivity to 5-FU. These results provide insights into the utilisation of ZST93 as an adjuvant or direct autophagy inhibitor and suggest ZST93 as a novel therapeutic strategy for treating CRC.

Keywords: Demethylzeylasteral (ZST93), colorectal cancer, apoptosis, autophagic flux, 5-fluorouracil (5-FU), chemosensitivity.

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[1]
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]
[2]
Maida, M.; Macaluso, F.S.; Ianiro, G.; Mangiola, F.; Sinagra, E.; Hold, G.; Maida, C.; Cammarota, G.; Gasbarrini, A.; Scarpulla, G. Screening of colorectal cancer: Present and future. Expert Rev. Anticancer Ther., 2017, 17(12), 1131-1146.
[http://dx.doi.org/10.1080/14737140.2017.1392243] [PMID: 29022408]
[3]
Dekker, E.; Tanis, P.J.; Vleugels, J.L.A.; Kasi, P.M.; Wallace, M.B. Colorectal cancer. Lancet, 2019, 394(10207), 1467-1480.
[http://dx.doi.org/10.1016/S0140-6736(19)32319-0] [PMID: 31631858]
[4]
Mármol, I.; Sánchez-de-Diego, C.; Pradilla Dieste, A.; Cerrada, E.; Rodriguez Yoldi, M.J. Colorectal carcinoma: A general overview and future perspectives in colorectal cancer. Int. J. Mol. Sci., 2017, 18(1), 197.
[http://dx.doi.org/10.3390/ijms18010197] [PMID: 28106826]
[5]
Due, S.L.; Wattchow, D.A.; Sweeney, J.L.; Milliken, L.; Luke, C.G. Colorectal cancer surgery 2000-2008: Evaluation of a prospective database. ANZ J. Surg., 2012, 82(6), 412-419.
[http://dx.doi.org/10.1111/j.1445-2197.2012.06078.x] [PMID: 22537147]
[6]
Kroemer, G.; Galluzzi, L.; Zitvogel, L.; Fridman, W.H. Colorectal cancer: The first neoplasia found to be under immunosurveillance and the last one to respond to immunotherapy? OncoImmunology, 2015, 4(7)e1058597
[http://dx.doi.org/10.1080/2162402X.2015.1058597] [PMID: 26140250]
[7]
Monkkonen, T.; Debnath, J. Inflammatory signaling cascades and autophagy in cancer. Autophagy, 2018, 14(2), 190-198.
[http://dx.doi.org/10.1080/15548627.2017.1345412] [PMID: 28813180]
[8]
Moore, J.S.; Aulet, T.H. Colorectal cancer screening. Surg. Clin. North Am., 2017, 97(3), 487-502.
[http://dx.doi.org/10.1016/j.suc.2017.01.001] [PMID: 28501242]
[9]
Magaji, B.A.; Moy, F.M.; Roslani, A.C.; Law, C.W. Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital. BMC Cancer, 2017, 17(1), 339.
[http://dx.doi.org/10.1186/s12885-017-3336-z] [PMID: 28521746]
[10]
Simon, K. Colorectal cancer development and advances in screening. Clin. Interv. Aging, 2016, 11, 967-976.
[http://dx.doi.org/10.2147/CIA.S109285] [PMID: 27486317]
[11]
Vogel, A.; Hofheinz, R.D.; Kubicka, S.; Arnold, D. Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies. Cancer Treat. Rev., 2017, 59, 54-60.
[http://dx.doi.org/10.1016/j.ctrv.2017.04.007] [PMID: 28738235]
[12]
Levine, B.; Kroemer, G. Biological functions of autophagy genes: A disease perspective. Cell, 2019, 176(1-2), 11-42.
[http://dx.doi.org/10.1016/j.cell.2018.09.048] [PMID: 30633901]
[13]
Townsend, K.N.; Hughson, L.R.; Schlie, K.; Poon, V.I.; Westerback, A.; Lum, J.J. Autophagy inhibition in cancer therapy: Metabolic considerations for antitumor immunity. Immunol. Rev., 2012, 249(1), 176-194.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01141.x] [PMID: 22889222]
[14]
Levy, J.M.M.; Towers, C.G.; Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer, 2017, 17(9), 528-542.
[http://dx.doi.org/10.1038/nrc.2017.53] [PMID: 28751651]
[15]
Lerena, C.; Calligaris, S.D.; Colombo, M.I. Autophagy: For better or for worse, in good times or in bad times. Curr. Mol. Med., 2008, 8(2), 92-101.
[http://dx.doi.org/10.2174/156652408783769634] [PMID: 18336290]
[16]
Gozuacik, D.; Kimchi, A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene, 2004, 23(16), 2891-2906.
[http://dx.doi.org/10.1038/sj.onc.1207521] [PMID: 15077152]
[17]
Liu, G.; Pei, F.; Yang, F.; Li, L.; Amin, A.D.; Liu, S.; Buchan, J.R.; Cho, W.C. Role of autophagy and apoptosis in non-small-cell lung cancer. Int. J. Mol. Sci., 2017, 18(2), 367.
[http://dx.doi.org/10.3390/ijms18020367] [PMID: 28208579]
[18]
Onorati, A.V.; Dyczynski, M.; Ojha, R.; Amaravadi, R.K. Targeting autophagy in cancer. Cancer, 2018, 124(16), 3307-3318.
[http://dx.doi.org/10.1002/cncr.31335] [PMID: 29671878]
[19]
D’Arcy, M.S. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol. Int., 2019, 43(6), 582-592.
[http://dx.doi.org/10.1002/cbin.11137] [PMID: 30958602]
[20]
Russo, M.; Russo, G.L. Autophagy inducers in cancer. Biochem. Pharmacol., 2018, 153, 51-61.
[http://dx.doi.org/10.1016/j.bcp.2018.02.007] [PMID: 29438677]
[21]
Li, Y.J.; Lei, Y.H.; Yao, N.; Wang, C.R.; Hu, N.; Ye, W.C.; Zhang, D.M.; Chen, Z.S. Autophagy and multidrug resistance in cancer. Chin. J. Cancer, 2017, 36(1), 52.
[http://dx.doi.org/10.1186/s40880-017-0219-2] [PMID: 28646911]
[22]
Bhat, P.; Kriel, J.; Priya, S.; Basappa, B.S.; Shivananju, N.S.; Loos, B. Modulating autophagy in cancer therapy: Advancements and challenges for cancer cell death sensitization. Biochem. Pharmacol., 2018, 147, 170-182.
[http://dx.doi.org/10.1016/j.bcp.2017.11.021] [PMID: 29203368]
[23]
Zhong, Z.; Sanchez-Lopez, E.; Karin, M. Autophagy, inflammation, and immunity: A troika governing cancer and its treatment. Cell, 2016, 166(2), 288-298.
[http://dx.doi.org/10.1016/j.cell.2016.05.051] [PMID: 27419869]
[24]
Sheng, J.; Qin, H.; Zhang, K.; Li, B.; Zhang, X. Targeting autophagy in chemotherapy-resistant of hepatocellular carcinoma. Am. J. Cancer Res., 2018, 8(3), 354-365.
[PMID: 29636994]
[25]
Kondo, Y.; Kanzawa, T.; Sawaya, R.; Kondo, S. The role of autophagy in cancer development and response to therapy. Nat. Rev. Cancer, 2005, 5(9), 726-734.
[http://dx.doi.org/10.1038/nrc1692] [PMID: 16148885]
[26]
Chen, C.H.; Hsieh, T.H.; Lin, Y.C.; Liu, Y.R.; Liou, J.P.; Yen, Y. Targeting autophagy by MPT0L145, a highly potent PIK3C3 inhibitor, provides synergistic interaction to targeted or chemotherapeutic agents in cancer cells. Cancers (Basel), 2019, 11(9), 1345.
[http://dx.doi.org/10.3390/cancers11091345] [PMID: 31514441]
[27]
Hasanain, M.; Sahai, R.; Pandey, P.; Maheshwari, M.; Choyal, K.; Gandhi, D.; Singh, A.; Singh, K.; Mitra, K.; Datta, D.; Sarkar, J. Microtubule disrupting agent-mediated inhibition of cancer cell growth is associated with blockade of autophagic flux and simultaneous induction of apoptosis. Cell Prolif., 2020, 53(4)e12749
[http://dx.doi.org/10.1111/cpr.12749] [PMID: 32167212]
[28]
Huang, Z.; Wang, T.; Xia, W.; Li, Q.; Chen, X.; Liu, X.; Wei, P.; Xu, W.; Lv, M. Oblongifolin C reverses GEM resistance via suppressing autophagy flux in bladder cancer cells. Exp. Ther. Med., 2020, 20(2), 1431-1440.
[http://dx.doi.org/10.3892/etm.2020.8856] [PMID: 32765672]
[29]
Elgendy, M.; Sheridan, C.; Brumatti, G.; Martin, S.J. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival. Mol. Cell, 2011, 42(1), 23-35.
[http://dx.doi.org/10.1016/j.molcel.2011.02.009] [PMID: 21353614]
[30]
Yang, C.; Wu, C.; Xu, D.; Wang, M.; Xia, Q. AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells. Biomed. Pharmacother., 2016, 81, 166-175.
[http://dx.doi.org/10.1016/j.biopha.2016.03.025] [PMID: 27261591]
[31]
Yao, C.W.; Kang, K.A.; Piao, M.J.; Ryu, Y.S.; Fernando, P.M.D.J.; Oh, M.C.; Park, J.E.; Shilnikova, K.; Na, S.Y.; Jeong, S.U.; Boo, S.J.; Hyun, J.W. Reduced autophagy in 5-fluorouracil resistant colon cancer cells. Biomol. Ther. (Seoul), 2017, 25(3), 315-320.
[http://dx.doi.org/10.4062/biomolther.2016.069] [PMID: 27737524]
[32]
Zhao, Y.; Hu, X.; Zuo, X.; Wang, M. Chemopreventive effects of some popular phytochemicals on human colon cancer: A review. Food Funct., 2018, 9(9), 4548-4568.
[http://dx.doi.org/10.1039/C8FO00850G] [PMID: 30118121]
[33]
Ganesan, K.; Jayachandran, M.; Xu, B. Diet-derived phytochemicals targeting colon cancer stem cells and microbiota in colorectal cancer. Int. J. Mol. Sci., 2020, 21(11), 3976.
[http://dx.doi.org/10.3390/ijms21113976] [PMID: 32492917]
[34]
Ji, X.; Peng, Q.; Wang, M. Anti-colon-cancer effects of polysaccharides: A mini-review of the mechanisms. Int. J. Biol. Macromol., 2018, 114, 1127-1133.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.03.186] [PMID: 29627471]
[35]
Davidson, K.T.; Zhu, Z.; Fang, Y. Phytochemicals in the fight against cancer. Pathol. Oncol. Res., 2016, 22(4), 655-660.
[http://dx.doi.org/10.1007/s12253-016-0045-x] [PMID: 26857640]
[36]
Yadav, N.; Parveen, S.; Banerjee, M. Potential of nano-phytochemicals in cervical cancer therapy. Clin. Chim. Acta, 2020, 505, 60-72.
[http://dx.doi.org/10.1016/j.cca.2020.01.035] [PMID: 32017926]
[37]
Arora, I.; Sharma, M.; Tollefsbol, T.O. Combinatorial epigenetics impact of polyphenols and phytochemicals in cancer prevention and therapy. Int. J. Mol. Sci., 2019, 20(18)E4567
[http://dx.doi.org/10.3390/ijms20184567] [PMID: 31540128]
[38]
An, H.; Zhu, Y.; Xu, W.; Liu, Y.; Zhang, J.; Lin, Z. Evaluation of immunosuppressive activity of demethylzeylasteral in a beagle dog kidney transplantation model. Cell Biochem. Biophys., 2015, 73(3), 673-679.
[http://dx.doi.org/10.1007/s12013-015-0684-7] [PMID: 27259309]
[39]
Xu, W.; Lin, Z.; Yang, C.; Zhang, Y.; Wang, G.; Xu, X.; Lv, Q.; Ren, Y.; Dong, Y. Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model. Int. Immunopharmacol., 2009, 9(7-8), 996-1001.
[http://dx.doi.org/10.1016/j.intimp.2009.04.007] [PMID: 19383554]
[40]
Zhao, Y.; He, J.; Li, J.; Peng, X.; Wang, X.; Dong, Z.; Zhao, E.; Liu, Y.; Wu, Z.; Cui, H. Demethylzeylasteral inhibits cell proliferation and induces apoptosis through suppressing MCL1 in melanoma cells. Cell Death Dis., 2017, 8(10)e3133
[http://dx.doi.org/10.1038/cddis.2017.529] [PMID: 29072681]
[41]
Wang, F.; Tian, X.; Zhang, Z.; Ma, Y.; Xie, X.; Liang, J.; Yang, C.; Yang, Y. Demethylzeylasteral (ZST93) inhibits cell growth and enhances cell chemosensitivity to gemcitabine in human pancreatic cancer cells via apoptotic and autophagic pathways. Int. J. Cancer, 2018, 142(9), 1938-1951.
[http://dx.doi.org/10.1002/ijc.31211] [PMID: 29238973]
[42]
Zhang, K.; Fu, G.; Pan, G.; Li, C.; Shen, L.; Hu, R.; Zhu, S.; Chen, Y.; Cui, H. Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis. Cell Death Dis., 2018, 9(10), 1035.
[http://dx.doi.org/10.1038/s41419-018-1086-8] [PMID: 30305611]
[43]
Li, L.; Ji, Y.; Fan, J.; Li, F.; Li, Y.; Wu, M.; Cheng, H.; Xu, C. Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways. Naunyn Schmiedebergs Arch. Pharmacol., 2019, 392(5), 593-603.
[http://dx.doi.org/10.1007/s00210-019-01614-5] [PMID: 30729271]
[44]
Schaaf, M.B.; Keulers, T.G.; Vooijs, M.A.; Rouschop, K.M. LC3/GABARAP family proteins: Autophagy-(un)related functions. FASEB J., 2016, 30(12), 3961-3978.
[http://dx.doi.org/10.1096/fj.201600698R] [PMID: 27601442]
[45]
Al-Ishaq, R.K.; Overy, A.J.; Büsselberg, D. Phytochemicals and gastrointestinal cancer: Cellular mechanisms and effects to change cancer progression. Biomolecules, 2020, 10(1), 105.
[http://dx.doi.org/10.3390/biom10010105] [PMID: 31936288]
[46]
Klionsky, D.J.; Boyer-Guittaut, M.; Bringer, M.A.; Lapaquette, P.; Lizard, G. Guidelines for the use and interpretation of assays for monitoring autophagy, 3rd edition; , 2012.
[http://dx.doi.org/10.4161/auto.19496]
[47]
Kimura, S.; Noda, T.; Yoshimori, T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy, 2007, 3(5), 452-460.
[http://dx.doi.org/10.4161/auto.4451] [PMID: 17534139]
[48]
Mizushima, N.; Yoshimori, T.; Levine, B. Methods in mammalian autophagy research. Cell, 2010, 140(3), 313-326.
[http://dx.doi.org/10.1016/j.cell.2010.01.028] [PMID: 20144757]
[49]
Wilde, L.; Tanson, K.; Curry, J.; Martinez-Outschoorn, U. Autophagy in cancer: A complex relationship. Biochem. J., 2018, 475(11), 1939-1954.
[http://dx.doi.org/10.1042/BCJ20170847] [PMID: 29891531]
[50]
Yang, W.; Jiang, C.; Xia, W.; Ju, H.; Jin, S.; Liu, S.; Zhang, L.; Ren, G.; Ma, H.; Ruan, M.; Hu, J. Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma. Cancer Lett., 2019, 451, 34-47.
[http://dx.doi.org/10.1016/j.canlet.2019.02.052] [PMID: 30862487]
[51]
Zhang, X.; Kumstel, S.; Jiang, K.; Meng, S.; Gong, P.; Vollmar, B.; Zechner, D. LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer. J. Adv. Res., 2019, 20, 9-21.
[http://dx.doi.org/10.1016/j.jare.2019.04.006] [PMID: 31193017]
[52]
Wen, Z.P.; Zeng, W.J.; Chen, Y.H.; Li, H.; Wang, J.Y.; Cheng, Q.; Yu, J.; Zhou, H.H.; Liu, Z.Z.; Xiao, J.; Chen, X.P. Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux. J. Exp. Clin. Cancer Res., 2019, 38(1), 298.
[http://dx.doi.org/10.1186/s13046-019-1287-8] [PMID: 31291988]
[53]
Oliveira, A.; Beyer, G.; Chugh, R.; Skube, S.J.; Majumder, K.; Banerjee, S.; Sangwan, V.; Li, L.; Dawra, R.; Subramanian, S.; Saluja, A.; Dudeja, V. Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F. Lab. Invest., 2015, 95(6), 648-659.
[http://dx.doi.org/10.1038/labinvest.2015.46] [PMID: 25893635]
[54]
Abate, M.; Festa, A.; Falco, M.; Lombardi, A.; Luce, A.; Grimaldi, A.; Zappavigna, S.; Sperlongano, P.; Irace, C.; Caraglia, M.; Misso, G. Mitochondria as playmakers of apoptosis, autophagy and senescence. Semin. Cell Dev. Biol., 2020, 98, 139-153.
[http://dx.doi.org/10.1016/j.semcdb.2019.05.022] [PMID: 31154010]
[55]
Kaminskyy, V.O.; Zhivotovsky, B. Free radicals in cross talk between autophagy and apoptosis. Antioxid. Redox Signal., 2014, 21(1), 86-102.
[http://dx.doi.org/10.1089/ars.2013.5746] [PMID: 24359220]
[56]
Kang, R.; Zeh, H.J.; Lotze, M.T.; Tang, D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ., 2011, 18(4), 571-580.
[http://dx.doi.org/10.1038/cdd.2010.191] [PMID: 21311563]
[57]
Sui, X.; Kong, N.; Ye, L.; Han, W.; Zhou, J.; Zhang, Q.; He, C.; Pan, H. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett., 2014, 344(2), 174-179.
[http://dx.doi.org/10.1016/j.canlet.2013.11.019] [PMID: 24333738]
[58]
Xia, X.; Wang, X.; Cheng, Z.; Qin, W.; Lei, L.; Jiang, J.; Hu, J. The role of pyroptosis in cancer: Pro-cancer or pro-“host”? Cell Death Dis., 2019, 10(9), 650.
[http://dx.doi.org/10.1038/s41419-019-1883-8] [PMID: 31501419]
[59]
Liu, W.; Wang, X.; Liu, Z.; Wang, Y.; Yin, B.; Yu, P.; Duan, X.; Liao, Z.; Chen, Y.; Liu, C.; Li, X.; Dai, Y.; Tao, Z. SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway. Br. J. Cancer, 2017, 117(8), 1139-1153.
[http://dx.doi.org/10.1038/bjc.2017.293] [PMID: 29017179]
[60]
Gonçalves, R.M.; Agnes, J.P.; Delgobo, M.; de Souza, P.O.; Thomé, M.P.; Heimfarth, L.; Lenz, G.; Moreira, J.C.F.; Zanotto-Filho, A. Late autophagy inhibitor chloroquine improves efficacy of the histone deacetylase inhibitor SAHA and temozolomide in gliomas. Biochem. Pharmacol., 2019, 163, 440-450.
[http://dx.doi.org/10.1016/j.bcp.2019.03.015] [PMID: 30878553]
[61]
Jung, O.; Lee, J.; Lee, Y.J.; Yun, J.M.; Son, Y.J.; Cho, J.Y.; Ryou, C.; Lee, S.Y. Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and β-catenin signaling pathways. Bioorg. Med. Chem. Lett., 2016, 26(16), 3963-3967.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.004] [PMID: 27422337]
[62]
Gomez-Cadena, A.; Urueña, C.; Prieto, K.; Martinez-Usatorre, A.; Donda, A.; Barreto, A.; Romero, P.; Fiorentino, S. Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model. Cell Death Dis., 2016, 7(6)e2243
[http://dx.doi.org/10.1038/cddis.2016.134] [PMID: 27253407]
[63]
Pan, H.; Wang, Y.; Na, K.; Wang, Y.; Wang, L.; Li, Z.; Guo, C.; Guo, D.; Wang, X. Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation. Cell Death Dis., 2019, 10(6), 456.
[http://dx.doi.org/10.1038/s41419-019-1653-7] [PMID: 31186406]
[64]
Zhou, N.; Wei, Z.X.; Qi, Z.X. Inhibition of autophagy triggers melatonin-induced apoptosis in glioblastoma cells. BMC Neurosci., 2019, 20(1), 63.
[http://dx.doi.org/10.1186/s12868-019-0545-1] [PMID: 31870319]
[65]
Vallecillo-Hernández, J.; Barrachina, M.D.; Ortiz-Masiá, D.; Coll, S.; Esplugues, J.V.; Calatayud, S.; Hernández, C. Indomethacin disrupts autophagic flux by inducing lysosomal dysfunction in gastric cancer cells and increases their sensitivity to cytotoxic drugs. Sci. Rep., 2018, 8(1), 3593.
[http://dx.doi.org/10.1038/s41598-018-21455-1] [PMID: 29483523]
[66]
Zhu, Z.; Zhang, P.; Li, N.; Kiang, K.M.Y.; Cheng, S.Y.; Wong, V.K.; Leung, G.K. Lovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells. BioMed Res. Int., 2019, 20192710693
[http://dx.doi.org/10.1155/2019/2710693] [PMID: 31662972]
[67]
Xu, C.; Wang, Y.; Tu, Q.; Zhang, Z.; Chen, M.; Mwangi, J.; Li, Y.; Jin, Y.; Zhao, X.; Lai, R. Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation. Oncogene, 2019, 38(11), 1832-1844.
[http://dx.doi.org/10.1038/s41388-018-0556-x] [PMID: 30356139]
[68]
Yoshida, G.J. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: From pathophysiology to treatment. J. Hematol. Oncol., 2017, 10(1), 67.
[http://dx.doi.org/10.1186/s13045-017-0436-9] [PMID: 28279189]
[69]
Feng, X.; Chen, L.; Guo, W.; Zhang, Y.; Lai, X.; Shao, L.; Li, Y. Graphene oxide induces p62/SQSTM-dependent apoptosis through the impairment of autophagic flux and lysosomal dysfunction in PC12 cells. Acta Biomater., 2018, 81, 278-292.
[http://dx.doi.org/10.1016/j.actbio.2018.09.057] [PMID: 30273743]
[70]
Zheng, K.; Li, Y.; Wang, S.; Wang, X.; Liao, C.; Hu, X.; Fan, L.; Kang, Q.; Zeng, Y.; Wu, X.; Wu, H.; Zhang, J.; Wang, Y.; He, Z. Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint. Autophagy, 2016, 12(9), 1593-1613.
[http://dx.doi.org/10.1080/15548627.2016.1192751] [PMID: 27310928]
[71]
Jiao, Y.N.; Wu, L.N.; Xue, D.; Liu, X.J.; Tian, Z.H.; Jiang, S.T.; Han, S.Y.; Li, P.P. Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells. Cancer Cell Int., 2018, 18, 149.
[http://dx.doi.org/10.1186/s12935-018-0646-4] [PMID: 30275772]
[72]
Zinnah, K.M.A.; Park, S.Y. Duloxetine enhances trail-mediated apoptosis via AMPK-mediated inhibition of autophagy flux in lung cancer cells. Anticancer Res., 2019, 39(12), 6621-6633.
[http://dx.doi.org/10.21873/anticanres.13877] [PMID: 31810927]
[73]
Rasheduzzaman, M.; Park, S.Y. Antihypertensive drug-candesartan attenuates TRAIL resistance in human lung cancer via AMPK-mediated inhibition of autophagy flux. Exp. Cell Res., 2018, 368(1), 126-135.
[http://dx.doi.org/10.1016/j.yexcr.2018.04.022] [PMID: 29694835]
[74]
Liao, C.; Zheng, K.; Li, Y.; Xu, H.; Kang, Q.; Fan, L.; Hu, X.; Jin, Z.; Zeng, Y.; Kong, X.; Zhang, J.; Wu, X.; Wu, H.; Liu, L.; Xiao, X.; Wang, Y.; He, Z. Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release. Oncotarget, 2016, 7(30), 47387-47402.
[http://dx.doi.org/10.18632/oncotarget.10159] [PMID: 27329722]
[75]
Pellerito, O.; Notaro, A.; Sabella, S.; De Blasio, A.; Vento, R.; Calvaruso, G.; Giuliano, M. WIN induces apoptotic cell death in human colon cancer cells through a block of autophagic flux dependent on PPARγ down-regulation. Apoptosis, 2014, 19(6), 1029-1042.
[http://dx.doi.org/10.1007/s10495-014-0985-0] [PMID: 24696378]

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