Curcumin-altered p53-response genes regulate radiosensitivity in p53-mutant Ewing's sarcoma cells

J. Veeraraghavan, M. Natarajan, T. S. Herman, Natarajan Aravindan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Aim: Curcumin has been demonstrated to have antitumor effects including radiosensitization by modulating many molecular targets including p53. Herein, we investigated the radiosensitizing effect of curcumin in p53 mutant Ewing's sarcoma (ES) cells. Materials and Methods: Cells exposed to radiation with or without curcumin were examined for transcriptional and translational levels of p53 downstream targets and its influence in regulated apoptosis, DNA fragmentation, cell survival and clonal expansion. Results: Curcumin significantly caused radiation induced expression of p21 and Bax, and reduced BclXl, Mcl1 with only marginal Bcl2 modulation. As a positive control to the study, both transcriptional and translational levels of p53 remained unchanged after radiation with/without curcumin. Conversely, curcumin caused radiation-induced apoptosis and DNA fragmentation. Consistently, curcumin enhanced radiation-induced cytotoxicity and clonal expansion. Conclusion: These results suggest that curcumin potentially radiosensitizes p53-mutant ES cells by regulating IR-modulated p53-response genes. However, the curcumin-associated p53-independent regulation of downstream targets remains to be explored.

Original languageEnglish (US)
Pages (from-to)4007-4015
Number of pages9
JournalAnticancer Research
Volume30
Issue number10
StatePublished - Oct 1 2010

Keywords

  • Apoptosis
  • Curcumin
  • Ewing's sarcoma
  • Radiosensitivity
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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