Temozolomide and carmustine cause large-scale heterochromatin reorganization in glioma cells

Biochemical and Biophysical Research Communications
Roberto PapaitElena Cattaneo

Abstract

Temozolomide (TMZ) and carmustine (BCNU), cancer-drugs usually used in the treatment of gliomas, are DNA-methylating agents producing O6-methylguanine. It has been shown that 06-methylguanine triggers DNA mismatch repair and in turn induce apoptosis and senescence, respectively, over a 4 and 6 days period [Y. Hirose, M.S. Berger, R.O. Pieper, p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells, Cancer Res. 61 (2001) 1957-1963; W. Roos, M. Baumgartner, B. Kaina, Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1, Oncogene 23 (2004) 359-367]. Here we show that TMZ and BCNU have an earlier effect on nuclear organization and chromatin structure. In particular, we report that TMZ and BCNU induce clustering of pericentromeric heterochromatin regions and increase the amount of heterochromatic proteins MeCP2 and HP1alpha bound to chromatin. These drugs also decrease global levels of histone H3 acetylation and increase levels of histone H3 trimethylated on lysine 9 (H3-triMeK9). These events precede the senescence status. We conclude that TMZ and BCNU efficacy in glioma treatment may implicate a ...Continue Reading

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Citations

Feb 23, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ching-Hsein ChenJen-Tsung Yang
Aug 18, 2010·Acta Neuropathologica·Markus J RiemenschneiderGuido Reifenberger
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Mar 23, 2011·International Journal of Cancer. Journal International Du Cancer·Jörg FelsbergUNKNOWN German Glioma Network
Apr 8, 2014·Genes, Chromosomes & Cancer·Vera RiehmerUNKNOWN German Glioma Network
Jun 24, 2014·Platelets·Jie ZhangKesheng Dai
Jan 1, 2011·Cancers·Irfan A Qureshi, Mark F Mehler
Apr 3, 2020·Cancers·Tareq SalehDavid A Gewirtz
Aug 8, 2019·Cancer Research·Lydia Robinson-GarciaJoanna I Loizou

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