p53 is involved in but not required for ionizing radiation-induced caspase-3 activation and apoptosis in human lymphoblast cell lines

Yongjia Yu, John B. Little

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

The caspase-3 has been shown to be involved in mediating apoptosis induced by different stimuli. However, it is still unclear whether p53 is required for the ionizing radiation (IR)-induced caspase-3 activation. In the present study, we examined IR-induced apoptosis in three closely related human lymphoblast cell lines that differ in p53 status. Irradiation of TK6 cells (wild-type p53) with 4 Gy γ-rays resulted in rapid apoptosis, whereas the apoptotic response was delayed and reduced in WTK1 cells (mutant p53) and the TK6 derivative line expressing HPV16 E6 (abrogated p53). The differential apoptotic responses in these cell lines correlated with caspase-3 activation. IR induced an early as well as a late phase of caspase-3 activation in TK6 but only a delayed onset in WTK1 and TK6-E6-5E cells. The early phase of caspase-3 activation coincided with an elevation of p53 and bax protein levels. Pretreatment of all three cell lines with a caspases inhibitor z- VAD-FMK inhibited apoptosis. These results suggest that IR-induced apoptosis is mediated by a mechanism involving the caspase-3 cascade, which is shared by both p53-dependent and -independent pathways. The activation of caspase-3 by IR may thus engage at least two separate mechanisms, one through the regulation of the bcl-2 family members by p53, whereas the other yet-to-be- identified one involves neither p53 nor bax.

Original languageEnglish (US)
Pages (from-to)4277-4281
Number of pages5
JournalCancer Research
Volume58
Issue number19
StatePublished - Oct 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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