European Journal of Cancer
Volume 46, Issue 2 , Pages 412-419 , January 2010

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

  • Esther P. Jane
    • ,
  • Ian F. Pollack

      Affiliations

    • Corresponding Author InformationCorresponding author: Address: Department of Neurosurgery, Children’s Hospital of Pittsburgh, 530, 45th Street, Pittsburgh, PA 15201, United States. Tel.: +1 412 692 5881; fax: +1 412 692 5921.

Received 16 June 2009 ,Revised 29 September 2009 ,Accepted 9 October 2009.

References 

  1. Maher EA, Furnari FB, Bachoo RM, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001;15(11):1311–1333
  2. Nagane M, Huang HJ, Cavenee WK. Advances in the molecular genetics of gliomas. Curr Opin Oncol. 1997;9(3):215–222
  3. Jane EP, Pollack IF. The heat shock protein antagonist 17-AAG potentiates the activity of enzastaurin against malignant human glioma cells. Cancer Lett. 2008;268(1):46–55
  4. Jane EP, Premkumar DR, Pollack IF. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther. 2006;319(3):1070–1080
  5. Jane EP, Premkumar DR, Pollack IF. 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. 2007;257(1):36–46
  6. Tanaka Y, Gavrielides MV, Mitsuuchi Y, Fujii T, Kazanietz MG. 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. 2003;278(36):33753–33762
  7. Bredel M, Pollack IF. 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). 1997;139(11):1000–1013
  8. Bredel M, Pollack IF, Freund JM, Rusnak J, Lazo JS. Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion. J Neurooncol. 1999;41(1):9–20
  9. Oh Y, Herbst RS, 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. 2008;26(7):1135–1141
  10. Rademaker-Lakhai JM, Beerepoot LV, 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. 2007;13(15 Pt 1):4474–4481
  11. Dent P, Yacoub A, Contessa J, et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res. 2003;159(3):283–300
  12. Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat Res. 2002;511(2):145–178
  13. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408(6811):433–439
  14. Paull TT, Rogakou EP, Yamazaki V, et al. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol. 2000;10(15):886–895
  15. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999;146(5):905–916
  16. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273(10):5858–5868
  17. Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S. MAPK pathways in radiation responses. Oncogene. 2003;22(37):5885–5896
  18. Wang X, McGowan CH, Zhao M, et al. Involvement of the MKK6–p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol. 2000;20(13):4543–4552
  19. Hayakawa J, Depatie C, Ohmichi M, 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. 2003;278(23):20582–20592
  20. Riss TLMR. Comparison of MTT, XTT and a novel tetrazolium compound MTS for in vitro proliferation and chemosensitivity assays. Mol Biol Cell. 1992;3:184
  21. Kotliarova S, Pastorino S, Kovell LC, et al. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation. Cancer Res. 2008;68(16):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. 2008;106(6):2436–2448
  23. Modesti M, Kanaar R. DNA repair: spot(light)s on chromatin. Curr Biol. 2001;11(6):R229–R232
  24. Redon C, Pilch D, Rogakou E, et al. Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev. 2002;12(2):162–169
  25. Carducci MA, Musib L, Kies MS, 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. 2006;24(25):4092–4099
  26. Keyes KA, Mann L, Sherman M, et al. LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice. Cancer Chemother Pharmacol. 2004;53(2):133–140
  27. Tabatabai G, Frank B, Wick A, et al. Synergistic antiglioma activity of radiotherapy and enzastaurin. Ann Neurol. 2007;61(2):153–161
  28. Graff JR, McNulty AM, Hanna KR, 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. 2005;65(16):7462–7469
  29. Lee KW, Kim SG, Kim HP, 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. 2008;68(6):1916–1926
  30. Moreau AS, Jia X, Ngo HT, et al. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. Blood. 2007;109(11):4964–4972
  31. Querfeld C, Rizvi MA, Kuzel TM, 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. 2006;126(7):1641–1647
  32. Olive PL. Detection of DNA damage in individual cells by analysis of histone H2AX phosphorylation. Method Cell Biol. 2004;75:355–373
  33. Ahn JY, Schwarz JK, Piwnica-Worms H, Canman CE. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 2000;60(21):5934–5936
  34. Furuta T, Takemura H, Liao ZY, 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. 2003;278(22):20303–20312
  35. Boldt S, Weidle UH, Kolch W. The role of MAPK pathways in the action of chemotherapeutic drugs. Carcinogenesis. 2002;23(11):1831–1838
  36. Ozaki I, Tani E, Ikemoto H, Kitagawa H, 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. 1999;274(9):5310–5317
  37. Zanke BW, Rubie EA, Winnett E, et al. Mammalian mitogen-activated protein kinase pathways are regulated through formation of specific kinase-activator complexes. J Biol Chem. 1996;271(47):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. 2008;582(18):2703–2708
  39. Sluss HK, Davis RJ. H2AX is a target of the JNK signaling pathway that is required for apoptotic DNA fragmentation. Mol Cell. 2006;23(2):152–153

PII: S0959-8049(09)00761-8

doi: 10.1016/j.ejca.2009.10.014

European Journal of Cancer
Volume 46, Issue 2 , Pages 412-419 , January 2010

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