N-formyl-3,4-methylenedioxy-benzylidene-γ-butyrolaetam, KNK437 induces caspase-3 activation through inhibition of mTORC1 activity in Cos-1 cells

Biochemical and Biophysical Research Communications

Volumn 395, Issue 1, 2010, Pages 56-60

  Inoue, Hirofumi ^a   Uyama, Takumi ^a   Hayashi, Junko ^a   Watanabe, Akito ^a   Kobayashi, Ken Ichi ^a   Tadokoro, Tadahiro ^a   Yamamoto, Yuji ^a  

^a TOKYO UNIVERSITY OF AGRICULTURE   (Japan)

Author keywords

Apoptosis; KNK437 (N formyl 3,4 methylenedioxybenzylidene c butyrolaetam); Mitochondria; mTOR; Raptor

Indexed keywords

ANTINEOPLASTIC AGENT; BENZYLIDENE DERIVATIVE; CASPASE 3; HEAT SHOCK PROTEIN 70; INSULIN; KNK 437; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; N FORMYL 3,4 METHYLENEDIOXY BENZYLIDENE GAMMA BUTYROLAETAM; TUBERIN; UNCLASSIFIED DRUG; 2 PYRROLIDONE DERIVATIVE; BENZHYDRYL DERIVATIVE; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; RAPTOR PROTEIN, HUMAN; SIGNAL PEPTIDE; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; APOPTOSIS; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; MITOCHONDRION; NONHUMAN; OUTER MEMBRANE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RAT; SIGNAL TRANSDUCTION; ANIMAL; BIOSYNTHESIS; CELL STRAIN COS1; CERCOPITHECUS; DRUG ANTAGONISM; METABOLISM;

MAMMALIA; RAPTORES;

ANIMALS; APOPTOSIS; BENZHYDRYL COMPOUNDS; CASPASE 3; CERCOPITHECUS AETHIOPS; COS CELLS; ENZYME ACTIVATION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEINS; PYRROLIDINONES; TUMOR SUPPRESSOR PROTEINS;

EID: 77951883212     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2010.03.134     Document Type: Article

References (36)

1. A. Soulard, M.N. Hall, Snapshot: mTOR signaling, Cell 129 (2007). 434.e431-432.e432.
2. D.C. Fingar, J. Blenis, Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression, Oncogene 23 (2004) 3151-3171.
3. S. Wullschleger, R. Loewith, M.N. Hall, TOR signaling in growth and metabolism, Cell 124 (2006) 471-484.
4. J. Urano, T. Sato, Y. Otsubo, M. Yamamoto, F. Tamanoi, Point mutations in TOR confer Rheb-independent growth in fission yeast and nutrient-independent mammalian TOR signaling in mammalian cells, Proc. Natl. Acad. Sci. USA 27 (2007) 3514-3519.
5. K. Hara, Y. Maruki, K. Yoshino, N. Oshiro, S. Hidayat, C. Tokunaga, J. Avruch, K. Yonezawa, Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action, Cell 26 (2002) 177-189.
6. H. Nojima, C. Tokunaga, S. Eguchi, N. Hidayat, K. Yoshino, K. Hara, N. Tanaka, J. Avruch, K. Yonezawa, The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif, J. Biol. Chem. 278 (2003) 15461-15464.
7. N. Oshiro, K. Yoshino, S. Hidayat, C. Tokunaga, K. Hara, S. Eguchi, J. Avruch, K. Yonezawa, Dissociation of raptor from mTOR is a mechanism of rapamycininduced inhibition of mTOR function, Genes Cells 9 (2004) 359-366.
8. G.G. Chiang, R.T. Abraham, Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase, J. Biol. Chem. 280 (2005) 25485-25490.
9. D.M. Sabatini, MTOR and cancer: insights into a complex relationship, Nat. Rev. Cancer 6 (2006) 729-734.
10. D.J. Price, J.R. Grove, V. Calvo, J. Avruch, B.E. Bierer, Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase, Science 257 (1992) 973-977.
11. J.K. Chen, J. Chen, G. Thomas, S.C. Kozma, R.C. Harris, S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy, Am. J. Physiol. Renal Physiol. 297 (2009) 585-593.
12. D.D. Sarbassov, S.M. Ali, D.H. Kim, D.A. Guertin, R.R. Latek, H. Erdjument-Bromage, P. Tempst, D.M. Sabatini, Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton, Curr. Biol. 27 (2004) 1296-1302.
13. E.J. Unlmann, W. Li, D.K. Scheidenhelm, C.L. Gau, F. Tamanoi, D.H. Gutmann, Loss of tuberous sclerosis complex 1 (TSC1) expression results in increased Rheb/S6K pathway signaling important for astrocyte cell size regulation, Glia 47 (2004) 180-188.
14. L.D. Aicher, J.S. Campbell, R.S. Yeung, Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis, J. Biol. Chem. 276 (2001) 21017-21021.
15. H.C. Dan, M. Sun, L. Yang, R.I. Feldman, X.M. Sui, C.C. Ou, M. Nellist, R.S. Yeung, D.J. Halley, S.V. Nicosia, W.J. Pledger, J.Q. Cheng, Phosphatidylinositol 3-kinase/AKT pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin, J. Biol. Chem. 277 (2002) 35364-35370.
16. S.L. Cai, A.R. Tee, J.D. Short, J.M. Bergeron, J. Kim, J. Shen, R. Guo, C.L. Johnson, K. Kiguchi, C.L. Walker, Activity of TSC2 is inhibited by Akt-mediated phosphorylation and membrane partitioning, J. Cell Biol. 172 (2006) 279-289.
17. M. Nellist, B. Verhaaf, M.A. Goedbloed, A.J. Reuser, A.M. van den Ouweland, D.J. Hally, TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex, Hum. Mol. Genet. 10 (2001) 2889-2898.
18. J.R. Sampson, Therapeutic targeting of mTOR in tuberous sclerosis, Biochem. Soc. Trans. 37 (2009) 259-264.
19. B.T. Nave, M. Ouwens, D.J. Withers, D.R. Alessi, P.R. Shepherd, Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation, Biochem. J. 344 (1999) 427-431.
20. S.R. von Manteuffel, P.B. Dennis, N. Pullen, A.C. Gingras, N. Sonenberg, G. Thomas, The insulin-induced signalling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycinsensitive point immediately upstream of p70s6k, Mol. Cell Biol. 17 (1997) 5426-5436.
21. U. Ozcan, L. Ozcan, E. Yilmaz, K. Düvel, M. Sahin, B.D. Manning, G.S. Hotamisligil, Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis, Mol. Cell 29 (2007) 541-551.
22. T. Kanazawa, I. Taneike, R. Akaishi, F. Yoshizawa, N. Furuya, S. Fujimura, M. Kadowaki, Amino acids and insulin control autophagic proteolysis through different signaling pathways in relation to mTOR in isolated rat hepatocytes, J. Biol. Chem. 279 (2004) 8452-8459.
23. L. Rachdi, N. Balcazar, F. Osorio-Duque, L. Elghazi, A. Weiss, A. Gould, K.J. Chang-Chen, M.J. Gambello, E. Bernal-Mizrachi, Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner, Proc. Natl. Acad. Sci. USA 105 (2008) 9250-9255.
24. M. Koishi, S. Yokota, T. Mae, Y. Nishimura, S. Kanamori, N. Horii, K. Shibuya, K. Sakai, M. Hiraoka, The effects of KNK437, a novel inhibitor of heat shock protein synthesis, on the acquisition of thermotolerance in murine transplantable tumor in vivo, Cancer Res. 7 (2001) 215-219.
25. S. Yokota, M. Kitahara, K. Nagata, Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells, Cancer Res. 60 (2000) 2942-2948.
26. R.K. Hansen, S. Oesterreich, P. Lemieux, K.D. Sarge, S.A. Fuqua, Quercetin inhibits heat shock protein induction but not heat shock factor DNA-binding in human breast carcinoma cells, Biochem. Biophys. Res. Commun. 239 (1997) 851-856.
27. J.A. Barnes, D.J. Dix, B.W. Collins, C. Luft, J.W. Allen, Expression of inducible Hsp70 enhances the proliferation of MCF-7 breast cancer cells and protects against the cytotoxic effects of hyperthermia, Cell Stress Chaperones 6 (2001) 316-325.
28. M. Jäättelä, Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells, Int. J. Cancer 60 (1995) 689-693.
29. H. Inoue, T. Uyama, T. Suzuki, M. Kazami, O. Hino, T. Kobayashi, K. Kobayashi, T. Tadokoro, Y. Yamamoto, Phosphorylated hamartin-Hsp70 complex regulates apoptosis via mitochondrial localization, Biochem. Biophys. Res. Commun. 391 (2010) 1148-1153.
30. T. Kobayashi, O. Minowa, Y. Sugitani, S. Takai, H. Mitani, E. Kobayashi, T. Noda, O. Hino, A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice, Proc. Natl. Acad. Sci. USA 98 (2001) 8762-8767.
31. S.M. Schieke, D. Phillips, J.P. McCoy Jr, A.M. Aponte, R.F. Shen, R.S. Balaban, T. Finkel, The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity, J. Biol. Chem. 281 (2006) 27643-27652.
32. S. Paglin, N.Y. Lee, C. Nakar, M. Fitzgerald, J. Plotkin, B. Deuel, N. Hackett, M. McMahill, E. Sphicas, N. Lampen, J. Yahalom, Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells, Cancer Res. 65 (2005) 11061-11070.
33. H. Hosoi, M.B. Dilling, T. Shikata, L.N. Liu, L. Shu, R.A. Ashmun, G.S. Germain, R.T. Abraham, P.J. Houghton, Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells, Cancer Res. 59 (1999) 886-894.
34. H. Inoue, M. Ndong, T. Suzuki, M. Kazami, T. Uyama, K. Kobayashi, T. Tadokoro, Y. Yamamoto, Hamartin-Hsp70 interaction is necessary for Akt-dependent tuberin phosphorylation during heat shock, Biosci. Biotech. Biochem. 73 (2009) 2488-2493.
35. H.G. Wendel, R.L. Silva, A. Malina, J.R. Mills, H. Zhu, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, J. Teruya-Feldstein, J. Pelletier, S.W. Lowe, Dissecting eIF4E action in tumorigenesis, Genes Dev. 21 (2007) 3232-3237.
36. A. Freilinger, M. Rosner, G. Krupitza, M. Nishino, G. Lubec, S.J. Korsmeyer, M. Hengstschläger, Tuberin activates the proapoptotic molecule BAD, Oncogene 25 (2006) 6467-6479.