Enzastaurin induces H2AX phosphorylation to regulate apoptosis via MAPK signalling in malignant glioma cells

European Journal of Cancer

Volumn 46, Issue 2, 2010, Pages 412-419

  Jane, Esther P ^a   Pollack, Ian F ^a  

^a UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

Apoptosis; Chk2; Enzastaurin; Glioma; H2AX; PKC

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; BISINDOLYLMALEIMIDE; CHECKPOINT KINASE 2; ENZASTAURIN; HISTONE H2AX; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN KINASE C; STAUROSPORINE;

APOPTOSIS; ARTICLE; CANCER CELL; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL GROWTH; CELL PROLIFERATION; CLONOGENIC ASSAY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; ENZYME INHIBITION; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; FLUORESCENCE MICROSCOPY; GLIOBLASTOMA; GROWTH INHIBITION; HUMAN; HUMAN CELL; IMMUNOCYTOCHEMISTRY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; DOSE-RESPONSE RELATIONSHIP, DRUG; GLIOMA; HISTONES; HUMANS; INDOLES; MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; STAT1 TRANSCRIPTION FACTOR;

EID: 72449169645     PISSN: 09598049     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejca.2009.10.014     Document Type: Article

References (39)

1. Maher E.A., Furnari F.B., Bachoo R.M., et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev 15 11 (2001) 1311-1333
2. Nagane M., Huang H.J., and Cavenee W.K. Advances in the molecular genetics of gliomas. Curr Opin Oncol 9 3 (1997) 215-222
3. Jane E.P., and Pollack I.F. The heat shock protein antagonist 17-AAG potentiates the activity of enzastaurin against malignant human glioma cells. Cancer Lett 268 1 (2008) 46-55
4. Jane E.P., Premkumar D.R., and Pollack I.F. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther 319 3 (2006) 1070-1080
5. Jane E.P., Premkumar D.R., and Pollack I.F. AG490 influences UCN-01-induced cytotoxicity in glioma cells in a p53-dependent fashion, correlating with effects on BAX cleavage and BAD phosphorylation. Cancer Lett 257 1 (2007) 36-46
6. Tanaka Y., Gavrielides M.V., Mitsuuchi Y., Fujii T., and Kazanietz M.G. Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. J Biol Chem 278 36 (2003) 33753-33762
7. Bredel M., and Pollack I.F. The role of protein kinase C (PKC) in the evolution and proliferation of malignant gliomas, and the application of PKC inhibition as a novel approach to anti-glioma therapy. Acta Neurochir (Wien) 139 11 (1997) 1000-1013
8. Bredel M., Pollack I.F., Freund J.M., Rusnak J., and Lazo J.S. Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion. J Neurooncol 41 1 (1999) 9-20
9. Oh Y., Herbst R.S., Burris H., et al. Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer. J Clin Oncol 26 7 (2008) 1135-1141
10. Rademaker-Lakhai J.M., Beerepoot L.V., Mehra N., et al. Phase I pharmacokinetic and pharmacodynamic study of the oral protein kinase C beta-inhibitor enzastaurin in combination with gemcitabine and cisplatin in patients with advanced cancer. Clin Cancer Res 13 15 Pt 1 (2007) 4474-4481
11. Dent P., Yacoub A., Contessa J., et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res 159 3 (2003) 283-300
12. Bernstein C., Bernstein H., Payne C.M., and Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat Res 511 2 (2002) 145-178
13. Zhou B.B., and Elledge S.J. The DNA damage response: putting checkpoints in perspective. Nature 408 6811 (2000) 433-439
14. Paull T.T., Rogakou E.P., Yamazaki V., et al. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10 15 (2000) 886-895
15. Rogakou E.P., Boon C., Redon C., and Bonner W.M. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146 5 (1999) 905-916
16. Rogakou E.P., Pilch D.R., Orr A.H., Ivanova V.S., and Bonner W.M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273 10 (1998) 5858-5868
17. Dent P., Yacoub A., Fisher P.B., Hagan M.P., and Grant S. MAPK pathways in radiation responses. Oncogene 22 37 (2003) 5885-5896
18. Wang X., McGowan C.H., Zhao M., et al. Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20 13 (2000) 4543-4552
19. Hayakawa J., Depatie C., Ohmichi M., and Mercola D. The activation of c-Jun NH2-terminal kinase (JNK) by DNA-damaging agents serves to promote drug resistance via activating transcription factor 2 (ATF2)-dependent enhanced DNA repair. J Biol Chem 278 23 (2003) 20582-20592
20. Riss T.L.M.R. Comparison of MTT, XTT and a novel tetrazolium compound MTS for in vitro proliferation and chemosensitivity assays. Mol Biol Cell 3 (1992) 184
21. Kotliarova S., Pastorino S., Kovell L.C., et al. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation. Cancer Res 68 16 (2008) 6643-6651
22. Rieger J., Lemke D., Maurer G., et al. Enzastaurin-induced apoptosis in glioma cells is caspase-dependent and inhibited by BCL-XL. J Neurochem 106 6 (2008) 2436-2448
23. Modesti M., and Kanaar R. DNA repair: spot(light)s on chromatin. Curr Biol 11 6 (2001) R229-R232
24. Redon C., Pilch D., Rogakou E., et al. Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev 12 2 (2002) 162-169
25. Carducci M.A., Musib L., Kies M.S., et al. Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J Clin Oncol 24 25 (2006) 4092-4099
26. Keyes K.A., Mann L., Sherman M., et al. LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice. Cancer Chemother Pharmacol 53 2 (2004) 133-140
27. Tabatabai G., Frank B., Wick A., et al. Synergistic antiglioma activity of radiotherapy and enzastaurin. Ann Neurol 61 2 (2007) 153-161
28. Graff J.R., McNulty A.M., Hanna K.R., et al. The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res 65 16 (2005) 7462-7469
29. Lee K.W., Kim S.G., Kim H.P., et al. Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric cancer cells. Cancer Res 68 6 (2008) 1916-1926
30. Moreau A.S., Jia X., Ngo H.T., et al. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. Blood 109 11 (2007) 4964-4972
31. Querfeld C., Rizvi M.A., Kuzel T.M., et al. The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway. J Invest Dermatol 126 7 (2006) 1641-1647
32. Olive P.L. Detection of DNA damage in individual cells by analysis of histone H2AX phosphorylation. Method Cell Biol 75 (2004) 355-373
33. Ahn J.Y., Schwarz J.K., Piwnica-Worms H., and Canman C.E. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 60 21 (2000) 5934-5936
34. Furuta T., Takemura H., Liao Z.Y., et al. Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J Biol Chem 278 22 (2003) 20303-20312
35. Boldt S., Weidle U.H., and Kolch W. The role of MAPK pathways in the action of chemotherapeutic drugs. Carcinogenesis 23 11 (2002) 1831-1838
36. Ozaki I., Tani E., Ikemoto H., Kitagawa H., and Fujikawa H. Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. J Biol Chem 274 9 (1999) 5310-5317
37. Zanke B.W., Rubie E.A., Winnett E., et al. Mammalian mitogen-activated protein kinase pathways are regulated through formation of specific kinase-activator complexes. J Biol Chem 271 47 (1996) 29876-29881
38. Lu C., Shi Y., Wang Z., et al. Serum starvation induces H2AX phosphorylation to regulate apoptosis via p38 MAPK pathway. FEBS Lett 582 18 (2008) 2703-2708
39. Sluss H.K., and Davis R.J. H2AX is a target of the JNK signaling pathway that is required for apoptotic DNA fragmentation. Mol Cell 23 2 (2006) 152-153