AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma

Oncology Reports

Volumn 31, Issue 2, 2014, Pages 649-656

  Hu, Min ^a   Huang, Haili ^a   Zhao, Rui ^b   Li, Peng ^a   Li, Mingyi ^a   Miao, Huilai ^a   Chen, Nianping ^a   Chen, Ming ^a  

^a GUANGDONG MEDICAL UNIVERSITY   (China)

^b SOUTHERN MEDICAL UNIVERSITY   (China)

Author keywords

AMPK; Autophagy; AZD8055; Hepatocellular carcinoma

Indexed keywords

3 METHYLADENINE; AUTOPHAGY PROTEIN 5; AZD 8055; CASPASE 3; CASPASE 9; CYCLIC AMP DEPENDENT PROTEIN KINASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGY; CANCER GROWTH; CANCER INHIBITION; CELL PROLIFERATION; CELL VACUOLE; COLONY FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; ENZYME ACTIVATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; LIGHT CHAIN; LIVER CELL CARCINOMA; PRIORITY JOURNAL; UPREGULATION;

ADENINE; AMP-ACTIVATED PROTEIN KINASES; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; CARCINOMA, HEPATOCELLULAR; CASPASES; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; ENZYME ACTIVATION; HUMANS; LIVER NEOPLASMS; MEMBRANE PROTEINS; MICROTUBULE-ASSOCIATED PROTEINS; MORPHOLINES; MULTIPROTEIN COMPLEXES; PHOSPHORYLATION; POLY(ADP-RIBOSE) POLYMERASES; SIGNAL TRANSDUCTION; SMALL UBIQUITIN-RELATED MODIFIER PROTEINS; TOR SERINE-THREONINE KINASES;

EID: 84892422431     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.2013.2890     Document Type: Article

References (29)

1. Sherman M: Epidemiology of hepatocellular carcinoma. Oncology 78 (Suppl 1): 7-10, 2010.
2. Tanaka M, Katayama F, Kato H, et al: Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol 21: 401-416, 2011.
3. Li S, Li Y, Hu R, et al: The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells. Oncol Lett 5: 717-721, 2013.
4. Chresta CM, Davies BR, Hickson I, et al: AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res 70: 288-298, 2010.
5. Holt SV, Logie A, Davies BR, et al: Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res 72: 1804-1813, 2012.
6. Levine B and Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6: 463-477, 2004.
7. Huang S, Yang ZJ, Yu C and Sinicrope FA: Inhibition of mTOR kinase by AZD8055 can antagonize chemotherapy-induced cell death through autophagy induction and down-regulation of p62/sequestosome 1. J Biol Chem 286: 40002-40012, 2011.
8. Sini P, James D, Chresta C and Guichard S: Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells. Autophagy 6: 553-554, 2010.
9. Willems L, Chapuis N, Puissant A, et al: The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 26: 1195-1202, 2012.
10. Huang HL, Zheng WL, Zhao R, Zhang B and Ma WL: FBXO31 is down-regulated and may function as a tumor suppressor in hepatocellular carcinoma. Oncol Rep 24: 715-720, 2010.
11. Strober W: Trypan blue exclusion test of cell viability. Curr Protoc Immunol Appendix 3: Appendix 3B, 2001.
12. Zhao R, Yan Q, Lv J, et al: CHD5, a tumor suppressor that is epigenetically silenced in lung cancer. Lung Cancer 76: 324-331, 2012.
13. Aoki H, Kondo Y, Aldape K, et al: Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy 4: 467-475, 2008.
14. Matsushita M, Suzuki NN, Obara K, Fujioka Y, Ohsumi Y and Inagaki F: Structure of Atg5.Atg16, a complex essential for autophagy. J Biol Chem 282: 6763-6772, 2007.
15. Pyo JO, Jang MH, Kwon YK, et al: Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 280: 20722-20729, 2005.
16. Seglen PO and Gordon PB: 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA 79: 1889-1892, 1982.
17. Wang CW and Klionsky DJ: The molecular mechanism of autophagy. Mol Med 9: 65-76, 2003.
18. Kondo Y, Kanzawa T, Sawaya R and Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 5: 726-734, 2005.
19. Bursch W, Hochegger K, Torok L, Marian B, Ellinger A and Hermann RS: Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci 113: 1189-1198, 2000.
20. Bursch W, Ellinger A, Gerner C, Frohwein U and Schulte-Hermann R: Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? Ann NY Acad Sci 926: 1-12, 2000.
21. Le XF, Mao W, Lu Z, Carter BZ and Bast RC Jr: Dasatinib induces autophagic cell death in human ovarian cancer. Cancer 116: 4980-4990, 2010.
22. Xiong HY, Guo XL, Bu XX, et al: Autophagic cell death induced by 5-FU in Bax or PUMA deficient human colon cancer cell. Cancer Lett 288: 68-74, 2010.
23. Fruman DA and Edinger AL: Cancer therapy: staying current with AMPK. Biochem J 412: e3-e5, 2008.
24. Ji C, Yang B, Yang YL, et al: Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition. Oncogene 29: 6557-6568, 2010.
25. Yun SM, Jung JH, Jeong SJ, Sohn EJ, Kim B and Kim SH: Tanshinone IIA induces autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and p70 S6K in KBM-5 leukemia cells. Phytother Res: Jun 27, 2013 (Epub ahead of print). doi: 10.1002/ptr.5015.
26. Puissant A, Robert G, Fenouille N, et al: Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 70: 1042-1052, 2010.
27. Chandrasekar B, Boylston WH, Venkatachalam K, Webster NJ, Prabhu SD and Valente AJ: Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-κB/PTEN suppression. J Biol Chem 283: 24889-24898, 2008.
28. Lee JW, Park S, Takahashi Y and Wang HG: The association of AMPK with ULK1 regulates autophagy. PLoS One 5: e15394, 2010.
29. Egan DF, Shackelford DB, Mihaylova MM, et al: Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331: 456-461, 2011.