Identification of dual mTORC1 and mTORC2 inhibitors in melanoma cells: Prodigiosin vs. obatoclax

Biochemical Pharmacology

Volumn 83, Issue 4, 2012, Pages 489-496

  Espona Fiedler, M ^a   Soto Cerrato, V ^a   Hosseini, A ^b   Lizcano, J M ^c   Guallar, V ^b   Quesada, R ^d   Gao, T ^e   Perez Tomas R ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b BARCELONA SUPERCOMPUTING CENTER   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^d UNIVERSITY OF BURGOS   (Spain)

^e UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Melanoma; mTOR complexes; mTOR inhibitors; Obatoclax; PI3K AKT; Prodigiosin

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; OBATOCLAX; PRODIGIOSIN; PROTEIN KINASE B;

ARTICLE; BINDING ASSAY; BINDING KINETICS; CANCER CHEMOTHERAPY; COMPUTER MODEL; CONTROLLED STUDY; DISEASE MODEL; DRUG ACTIVITY; DRUG MECHANISM; HUMAN; HUMAN CELL; INFORMATION PROCESSING; MELANOMA CELL; MOLECULARLY TARGETED THERAPY; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; SURFACE PLASMON RESONANCE;

ANTI-BACTERIAL AGENTS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INSULIN RECEPTOR SUBSTRATE PROTEINS; MELANOMA; PHOSPHATIDYLINOSITOL 3-KINASES; PRODIGIOSIN; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PYRROLES; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; TRANSCRIPTION FACTORS;

EID: 84855802012     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2011.11.027     Document Type: Article

References (33)

1. R. Perez-Tomas, and M. Vinas New insights on the antitumoral properties of prodiginines Curr Med Chem 17 2010 2222 2231
2. V. Soto-Cerrato, F. Vinals, J.R. Lambert, J.A. Kelly, and R. Perez-Tomas Prodigiosin induces the proapoptotic gene NAG-1 via glycogen synthase kinase-3beta activity in human breast cancer cells Mol Cancer Ther 6 2007 362 369 (Pubitemid 46206701)
3. M. Nguyen, R.C. Marcellus, A. Roulston, M. Watson, L. Serfass, and S.R. Murthy Madiraju Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis Proc Natl Acad Sci U S A 104 2007 19512 19517
4. D.D. Sarbassov, S.M. Ali, D.H. Kim, D.A. Guertin, R.R. Latek, and H. Erdjument-Bromage Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton Curr Biol 14 2004 1296 1302 (Pubitemid 38991819)
5. S. Wullschleger, R. Loewith, and M.N. Hall TOR signaling in growth and metabolism Cell 124 2006 471 484 (Pubitemid 43199434)
6. D.A. Guertin, and D.M. Sabatini The pharmacology of mTOR inhibition Sci Signal 2 2009 pe24
7. S.M. Ali, and D.M. Sabatini Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site J Biol Chem 280 2005 19445 19448 (Pubitemid 41379463)
8. M. Frodin, T.L. Antal, B.A. Dummler, C.J. Jensen, M. Deak, and S. Gammeltoft A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation EMBO J 21 2002 5396 5407 (Pubitemid 35231019)
9. J.M. Garcia-Martinez, and D.R. Alessi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1) Biochem J 416 2008 375 385
10. D.R. Alessi, M. Andjelkovic, B. Caudwell, P. Cron, N. Morrice, and P. Cohen Mechanism of activation of protein kinase B by insulin and IGF-1 EMBO J 15 1996 6541 6551 (Pubitemid 26413787)
11. B.D. Manning, and L.C. Cantley AKT/PKB signaling: navigating downstream Cell 129 2007 1261 1274 (Pubitemid 46962095)
12. T. Schmelzle, and M.N. Hall TOR, a central controller of cell growth Cell 103 2000 253 262
13. D.C. Fingar, S. Salama, C. Tsou, E. Harlow, and J. Blenis Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E Genes Dev 16 2002 1472 1487 (Pubitemid 34686329)
14. K. Hara, Y. Maruki, X. Long, K. Yoshino, N. Oshiro, and S. Hidayat Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action Cell 110 2002 177 189 (Pubitemid 34876546)
15. D.H. Kim, D.D. Sarbassov, S.M. Ali, J.E. King, R.R. Latek, and H. Erdjument-Bromage mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery Cell 110 2002 163 175 (Pubitemid 34876545)
16. Y. Sancak, C.C. Thoreen, T.R. Peterson, R.A. Lindquist, S.A. Kang, and E. Spooner PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase Mol Cell 25 2007 903 915 (Pubitemid 46436534)
17. H.B. Jefferies, S. Fumagalli, P.B. Dennis, C. Reinhard, R.B. Pearson, and G. Thomas Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k EMBO J 16 1997 3693 3704 (Pubitemid 27250062)
18. S. Huang, and P.J. Houghton Targeting mTOR signaling for cancer therapy Curr Opin Pharmacol 3 2003 371 377 (Pubitemid 36908940)
19. X. Wan, B. Harkavy, N. Shen, P. Grohar, and L.J. Helman Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism Oncogene 26 2007 1932 1940 (Pubitemid 46474636)
20. A. Carracedo, L. Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, and A. Alimonti Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer J Clin Invest 118 2008 3065 3074
21. J. Liu, P.D. Stevens, and T. Gao mTOR-dependent regulation of PHLPP expression controls the rapamycin sensitivity in cancer cells J Biol Chem 286 8 2011 6510 6520
22. H. Nordin, M. Jungnelius, R. Karlsson, and O.P. Karlsson Kinetic studies of small molecule interactions with protein kinases using biosensor technology Anal Biochem 340 2005 359 368 (Pubitemid 40544876)
23. Glide version 5.6, Schrödinger 2010 LLC New York, NY
24. M.E. Feldman, B. Apsel, A. Uotila, R. Loewith, Z.A. Knight, and D. Ruggero Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2 PLOS Biol 7 2009 371 383
25. K. Borrelli, B. Cossins, and V. Guallar Exploring hierarchical refinement techniques for induced fit docking with protein and ligand flexibility J Comput Chem 31 2010 1224 1235
26. A.J. Miller, and M.C. Mihm Jr. Melanoma N Engl J Med 355 2006 51 65
27. J. Pan, C. Cheng, S. Verstovsek, Q. Chen, Y. Jin, and Q. Cao The BH3-mimetic GX15-070 induces autophagy, potentiates the cytotoxicity of carboplatin and 5-fluorouracil in esophageal carcinoma cells Cancer Lett 293 2010 167 174
28. Y. Kabeya, N. Mizushima, A. Yamamoto, S. Oshitani-Okamoto, Y. Ohsumi, and T. Yoshimori LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation J Cell Sci 117 2004 2805 2812 (Pubitemid 38997262)
29. K.N. Dalby, N. Morrice, F.B. Caudwell, J. Avruch, and P. Cohen Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK J Biol Chem 273 1998 1496 1505 (Pubitemid 28133672)
30. M. Hanada, J. Feng, and B.A. Hemmings Structure, regulation and function of PKB/AKT - a major therapeutic target Biochim Biophys Acta 1697 2004 3 16 (Pubitemid 38326757)
31. M.M. Tirion Large amplitude elastic motions in proteins from a single-parameter, atomic analysis Phys Rev Lett 77 1996 1905 1908 (Pubitemid 126625816)
32. C.C. Jiang, D. Wroblewski, F. Yang, P. Hersey, and X.D. Zhang Human melanoma cells under endoplasmic reticulum stress are more susceptible to apoptosis induced by the BH3 mimetic obatoclax Neoplasia 11 9 2009 945 955
33. Q. Liu, C. Throreen, J. Wang, D. Sabatini, and N.S. Gray mTOR mediated anti-cancer drug discovery Drug Discov Today Ther Strateg 6 2009 47 55