Sensitization to UV-induced apoptosis by the histone deacetylase inhibitor trichostatin A (TSA)

Myoung Sook Kim, Jin Hyen Baek, Devulapalli Chakravarty, David Sidransky, France Carrier

Research output: Contribution to journalArticlepeer-review

Abstract

UV-induced apoptosis is a protective mechanism that is primarily caused by DNA damage. Cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts are the main DNA adducts triggered by UV radiation. Because the formation of DNA lesions in the chromatin is modulated by the structure of the nucleosomes, we postulated that modification of chromatin compaction could affect the formation of the lesions and consequently apoptosis. To verify this possibility we treated human colon carcinoma RKO cells with the histone deacetylase inhibitor trichostatin A (TSA) prior to exposure to UV radiation. Our data show that pre-treatment with TSA increased UV killing efficiency by more than threefold. This effect correlated with increased formation of CPDs and consequently apoptosis. On the other hand, TSA treatment after UV exposure rather than before had no more effect than UV radiation alone. This suggests that a primed (opened) chromatin status is required to sensitize the cells. Moreover, TSA sensitization to UV-induced apoptosis is p53 dependent. p53 and acetylation of the core histones may thus contribute to UV-induced apoptosis by modulating the formation of DNA lesions on chromatin.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalExperimental cell research
Volume306
Issue number1
DOIs
StatePublished - May 15 2005

Keywords

  • Apoptosis
  • Histone acetylation
  • UV
  • p53

ASJC Scopus subject areas

  • Cell Biology

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