Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy

International Journal of Molecular Medicine

Volumn 31, Issue 6, 2013, Pages 1449-1456

  Chang, Zhexing ^a   Shi, Guang ^b   Jin, Jiqiang ^c   Guo, Huatao ^a   Guo, Xuefeng ^a   Luo, Fangyue ^a   Song, Yuguo ^a   Jia, Xiaojing ^b  

^a Department of Dermatology   (China)

^b THE SECOND HOSPITAL OF JILIN UNIVERSITY   (China)

^c Jilin Province   (China)

Author keywords

Apoptosis; Autophagy; Hepatocellular carcinoma; NVP BEZ235; PI3K AKT mTOR

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; AUTOPHAGY PROTEIN 5; CELL PROTEIN; PROTEIN LC3 II; PROTEIN P62; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL; CANCER INHIBITION; CONTROLLED STUDY; DRUG MECHANISM; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; WESTERN BLOTTING;

ADENINE; APOPTOSIS; AUTOPHAGY; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL PROLIFERATION; HUMANS; IMIDAZOLES; LIVER NEOPLASMS; MICROTUBULE-ASSOCIATED PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASES; QUINOLINES; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84876397501     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2013.1351     Document Type: Article

References (35)

1. El-Serag HB and Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132: 2557-2576, 2007. (Pubitemid 46890874)
2. Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin 62: 10-29, 2012.
3. Verslype C, Van Cutsem E, Dicato M, et al: The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008. Ann Oncol 20 (Suppl 7): vii1-vii6, 2009.
4. Sia D and Villanueva A: Signaling pathways in hepatocellular carcinoma. Oncology 81 (Suppl 1): S18-S23, 2011.
5. Vivanco I and Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2: 489-501, 2002. (Pubitemid 37328931)
6. Luo J, Manning BD and Cantley LC: Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4: 257-262, 2003. (Pubitemid 37329790)
7. Sabatini DM: mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6: 729-734, 2006. (Pubitemid 44286004)
8. Kong D and Yamori T: Advances in development of phosphatidylinositol 3-kinase inhibitors. Curr Med Chem 16: 2839-2854, 2009.
9. Pang RW and Poon RT: From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. Oncology 72 (Suppl 1): S30-S44, 2007.
10. Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature 451: 1069-1075, 2008. (Pubitemid 351317450)
11. Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell 132: 27-42, 2008.
12. Rubinsztein DC, Gestwicki JE, Murphy LO and Klionsky DJ: Potential therapeutic applications of autophagy. Nat Rev Drug Discov 6: 304-312, 2007. (Pubitemid 46505881)
13. Masuda M, Shimomura M, Kobayashi K, et al: Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular carcinoma cell lines. Oncol Rep 26: 1273-1279, 2011.
14. Thomas HE, Mercer CA, Carnevalli LS, et al: mTOR inhibitors synergize on regression, reversal of gene expression, and autophagy in hepatocellular carcinoma. Sci Transl Med 4: 139-184, 2012.
15. Herrera VA, Zeindl-Eberhart E, Jung A, et al: The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines. Anticancer Res 31: 849-854, 2011.
16. Shire AM and Roberts LR: Prevention of hepatocellular carcinoma: progress and challenges. Minerva Gastroenterol Dietol 58: 49-64, 2012.
17. Sandhu DS, Tharayil VS, Lai JP and Roberts LR: Treatment options for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2: 81-92, 2008.
18. Roberts LR and Gores GJ: Emerging drugs for hepatocellular carcinoma. Expert Opin Emerg Drugs 11: 469-487, 2006. (Pubitemid 44386371)
19. Tokunaga E, Oki E, Egashira A, et al: Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets 8: 27-36, 2008. (Pubitemid 351237907)
20. Zou CY, Smith KD, Zhu QS, et al: Dual targeting of AKT and mammalian target of rapamycin: a potential therapeutic approach for malignant peripheral nerve sheath tumor. Mol Cancer Ther 8: 1157-1168, 2009.
21. Xu CX, Zhao L, Yue P, et al: Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells by blockage of autophagy. Cancer Biol Ther 12: 549-555, 2011.
22. Mirzoeva OK, Hann B, Hom YK, et al: Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma. J Mol Med 89: 877-889, 2011.
23. Jung CH, Jun CB, Ro SH, et al: ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20: 1992-2003, 2009.
24. Fujiwara K, Iwado E, Mills GB, et al: Akt inhibitor shows anticancer and radiosensitizing effects in malignant glioma cells by inducing autophagy. Int J Oncol 31: 753-760, 2007.
25. Yang S, Xiao X, Meng X and Leslie KK: A mechanism for synergy with combined mTOR and PI3 kinase inhibitors. PLoS One 6: e26343, 2011.
26. Danial NN and Korsmeyer SJ: Cell death: critical control points. Cell 116: 205-219, 2004. (Pubitemid 38167313)
27. Levine B and Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6: 463-477, 2004. (Pubitemid 38456176)
28. Mizushima N and Klionsky DJ: Protein turnover via autophagy: implications for metabolism. Annu Rev Nutr 27: 19-40, 2007. (Pubitemid 351373346)
29. Eisenberg-Lerner A, Bialik S, Simon HU and Kimchi A: Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ 16: 966-975, 2009.
30. Yang Y, Xing D, Zhou F and Chen Q: Mitochondrial autophagy protects against heat shock-induced apoptosis through reducing cytosolic cytochrome c release and downstream caspase-3 activation. Biochem Biophys Res Commun 395: 190-195, 2010.
31. Zhuang W, Qin Z and Liang Z: The role of autophagy in sensitizing malignant glioma cells to radiation therapy. Acta Biochim Biophys Sin 41: 341-351, 2009.
32. White E and DiPaola RS: The double-edged sword of autophagy modulation in cancer. Clin Cancer Res 15: 5308-5316, 2009.
33. Dikic I, Johansen T and Kirkin V: Selective autophagy in cancer development and therapy. Cancer Res 70: 3431-3434, 2010.
34. Nguyen TM, Subramanian IV, Xiao X, et al: Endostatin induces autophagy in endothelial cells by modulating Beclin 1 and beta-catenin levels. J Cell Mol Med 13: 3687-3698, 2009.
35. Nguyen TM, Subramanian IV, Kelekar A and Ramakrishnan S: Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells. Blood 109: 4793-4802, 2007. (Pubitemid 46827773)