Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells

Biochemical Pharmacology

Volumn 84, Issue 9, 2012, Pages 1154-1163

  Singh, Brahma N ^a   Kumar, Dhruv ^a   Shankar, Sharmila ^a   Srivastava, Rakesh K ^a  

^a UNIVERSITY OF KANSAS CANCER CENTER   (United States)

Author keywords

AKT; Apoptosis; Atg7; Autophagy; Beclin1; Pancreatic cancer; PI3K; Rottlerin

Indexed keywords

3 METHYLADENINE; BECLIN 1; CASPASE 3; CASPASE 9; MAMMALIAN TARGET OF RAPAMYCIN; MEMBRANE PROTEIN; MICROTUBULE ASSOCIATED PROTEIN LC3 I; MICROTUBULE ASSOCIATED PROTEIN LC3 II; PHENAZINE METHOSULFATE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; PUROMYCIN; RAPAMYCIN; ROTTLERIN; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS;

APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL CULTURE; CANCER STEM CELL; CELL SURVIVAL; CELL VACUOLE; DOSE RESPONSE; DRUG EXPOSURE; ELECTRON MICROSCOPE; ENZYME ACTIVATION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IMMUNOCYTOCHEMISTRY; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION;

ACETOPHENONES; ANTINEOPLASTIC AGENTS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; BENZOPYRANS; CASPASE 3; CASPASE 9; CELL LINE, TUMOR; CELL SURVIVAL; ENZYME ACTIVATION; HUMANS; MEMBRANE PROTEINS; NEOPLASTIC STEM CELLS; PANCREATIC NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; UBIQUITIN-ACTIVATING ENZYMES;

EID: 84866614835     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2012.08.007     Document Type: Article

References (47)

1. Z. Yue, S. Jin, C. Yang, A.J. Levine, and N. Heintz Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor Proc Natl Acad Sci USA 100 2003 15077 15082
2. V. Deretic, M. Delgado, I. Vergne, S. Master, S. De Haro, and M. Ponpuak Autophagy in immunity against mycobacterium tuberculosis: a model system to dissect immunological roles of autophagy Curr Top Microbiol Immunol 335 2009 169 188
3. M.C. Maiuri, E. Zalckvar, A. Kimchi, and G. Kroemer Self-eating and self-killing: crosstalk between autophagy and apoptosis Nat Rev Mol Cell Biol 8 2007 741 752
4. B. Levine, and G. Kroemer Autophagy in the pathogenesis of disease Cell 132 2008 27 42
5. K.M. Livesey, D. Tang, H.J. Zeh, and M.T. Lotze Autophagy inhibition in combination cancer treatment Curr Opin Investig Drugs 10 2009 1269 1279
6. N. Taguchi-Atarashi, M. Hamasaki, K. Matsunaga, H. Omori, N.T. Ktistakis, and T. Yoshimori Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy Traffic 11 2010 468 478
7. U. Akar, B. Ozpolat, K. Mehta, J. Fok, Y. Kondo, and G. Lopez-Berestein Tissue transglutaminase inhibits autophagy in pancreatic cancer cells Mol Cancer Res 5 2007 241 249
8. R. Lock, and J. Debnath Ras, autophagy and glycolysis Cell Cycle 10 2011 1516 1517
9. Z.J. Yang, C.E. Chee, S. Huang, and F.A. Sinicrope The role of autophagy in cancer: therapeutic implications Mol Cancer Ther 10 2011 1533 1541
10. V. Espina, B.D. Mariani, R.I. Gallagher, K. Tran, S. Banks, and J. Wiedemann Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival PLoS One 5 2010 e10240
11. J. Geng, M. Baba, U. Nair, and D.J. Klionsky Quantitative analysis of autophagy-related protein stoichiometry by fluorescence microscopy J Cell Biol 182 2008 129 140
12. T. Nemoto, I. Tanida, E. Tanida-Miyake, N. Minematsu-Ikeguchi, M. Yokota, and M. Ohsumi The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification J Biol Chem 278 2003 39517 39526
13. N. Mizushima, A. Yamamoto, M. Hatano, Y. Kobayashi, Y. Kabeya, and K. Suzuki Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells J Cell Biol 152 2001 657 668
14. X. Qu, J. Yu, G. Bhagat, N. Furuya, H. Hibshoosh, and A. Troxel Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene J Clin Invest 112 2003 1809 1820
15. A. Ropolo, D. Grasso, R. Pardo, M.L. Sacchetti, C. Archange, and A. Lo Re The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells J Biol Chem 282 2007 37124 37133
16. T.M. Nguyen, I.V. Subramanian, A. Kelekar, and S. Ramakrishnan Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells Blood 109 2007 4793 4802
17. B. Levine, and J. Yuan Autophagy in cell death: an innocent convict J Clin Invest 115 2005 2679 2688
18. M.R. Alison, S.M. Lim, and L.J. Nicholson Cancer stem cells: problems for therapy J Pathol 223 2011 147 161
19. E.V. Batrakova, H.E. Gendelman, and A.V. Kabanov Cell-mediated drug delivery Expert Opin Drug Deliv 8 2011 415 433
20. S. Shankar, D. Nall, S.N. Tang, D. Meeker, J. Passarini, and J. Sharma Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition PLoS One 6 2011 e16530
21. A.M. Martelli, C. Evangelisti, M.Y. Follo, G. Ramazzotti, M. Fini, and R. Giardino Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cells Curr Med Chem 18 2011 2715 2726
22. M. Gschwendt, H.J. Muller, K. Kielbassa, R. Zang, W. Kittstein, and G. Rincke Rottlerin, a novel protein kinase inhibitor Biochem Biophys Res Commun 199 1994 93 98
23. K.S. Song, J.S. Kim, E.J. Yun, Y.R. Kim, K.S. Seo, and J.H. Park Rottlerin induces autophagy and apoptotic cell death through a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells: the protective role of autophagy in apoptosis Autophagy 4 2008 650 658
24. S.P. Soltoff Rottlerin is a mitochondrial uncoupler that decreases cellular ATP levels and indirectly blocks protein kinase Cdelta tyrosine phosphorylation J Biol Chem 276 2001 37986 37992
25. S. Saiki, Y. Sasazawa, Y. Imamichi, S. Kawajiri, T. Fujimaki, and I. Tanida Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition Autophagy 7 2011 176 187
26. M. Wiznerowicz, and D. Trono Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference J Virol 77 2003 8957 8961
27. Q. Chen, S. Ganapathy, K.P. Singh, S. Shankar, and R.K. Srivastava Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells PLoS One 5 2010 e15288
28. J.J. Lum, D.E. Bauer, M. Kong, M.H. Harris, C. Li, and T. Lindsten Growth factor regulation of autophagy and cell survival in the absence of apoptosis Cell 120 2005 237 248
29. R.A. Gonzalez-Polo, P. Boya, A.L. Pauleau, A. Jalil, N. Larochette, and S. Souquere The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death J Cell Sci 118 2005 3091 3102
30. N. Mizushima, A. Yamamoto, M. Matsui, T. Yoshimori, and Y. Ohsumi In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker Mol Biol Cell 15 2004 1101 1111
31. P.O. Seglen, and P.B. Gordon 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes Proc Natl Acad Sci USA 79 1982 1889 1892
32. K. Asanuma, I. Tanida, I. Shirato, T. Ueno, H. Takahara, and T. Nishitani MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis FASEB J 17 2003 1165 1167
33. B. Ozpolat, U. Akar, K. Mehta, and G. Lopez-Berestein PKC delta and tissue transglutaminase are novel inhibitors of autophagy in pancreatic cancer cells Autophagy 3 2007 480 483
34. J.S. Kruger, and K.B. Reddy Distinct mechanisms mediate the initial and sustained phases of cell migration in epidermal growth factor receptor-overexpressing cells Mol Cancer Res 1 2003 801 809
35. Y. Shao, Z. Gao, P.A. Marks, and X. Jiang Apoptotic and autophagic cell death induced by histone deacetylase inhibitors Proc Natl Acad Sci USA 101 2004 18030 18035
36. S.K. Roy, R.K. Srivastava, and S. Shankar Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer J Mol Signal 5 2010 10
37. X. Chen, H. Thakkar, F. Tyan, S. Gim, H. Robinson, and C. Lee Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer Oncogene 20 2001 6073 6083
38. K.E. O'Reilly, F. Rojo, Q.B. She, D. Solit, G.B. Mills, and D. Smith mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res 66 2006 1500 1508
39. A.O. de Graaf, T. de Witte, and J.H. Jansen Inhibitor of apoptosis proteins: new therapeutic targets in hematological cancer Leukemia 18 2004 1751 1759
40. B. Levine Eating oneself and uninvited guests: autophagy-related pathways in cellular defense Cell 120 2005 159 162
41. D. Kessel, J.J. Reiners Jr., S.T. Hazeldine, L. Polin, and J.P. Horwitz The role of autophagy in the death of L1210 leukemia cells initiated by the new antitumor agents, XK469 and SH80 Mol Cancer Ther 6 2007 370 379
42. M. Gaytan, C. Morales, J.E. Sanchez-Criado, and F. Gaytan Immunolocalization of beclin 1, a bcl-2-binding, autophagy-related protein, in the human ovary: possible relation to life span of corpus luteum Cell Tissue Res 331 2008 509 517
43. X.H. Liang, S. Jackson, M. Seaman, K. Brown, B. Kempkes, and H. Hibshoosh Induction of autophagy and inhibition of tumorigenesis by beclin 1 Nature 402 1999 672 676
44. W.L. Sun, J. Chen, Y.P. Wang, and H. Zheng Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development Autophagy 7 2011 1035 1044
45. D.J. Klionsky, Z. Elazar, P.O. Seglen, and D.C. Rubinsztein Does bafilomycin A1 block the fusion of autophagosomes with lysosomes Autophagy 4 2008 849 950
46. S.P. Davies, H. Reddy, M. Caivano, and P. Cohen Specificity and mechanism of action of some commonly used protein kinase inhibitors Biochem J 351 2000 95 105
47. S.P. Soltoff Rottlerin: an inappropriate and ineffective inhibitor of PKCdelta Trends Pharmacol Sci 28 2007 453 458