DNA damage-mediated apoptosis induced by selenium compounds

Nai Zhou, Hai Xiao, Tsai Kun Li, Alam Nur-E-Kamal, Leroy-Fong Liu

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Selenium (Se) compounds, which are the most extensively studied cancer chemopreventive agents, induce apoptotic death of tumor cells. In the current study, we show that selenite-induced apoptosis involves DNA damage. We showed that selenite-induced apoptosis as evidenced by cleavage of poly(ADP-ribose) polymerase was reduced in NIH 3T3 cells treated with ATM small interfering RNA, suggesting the involvement of the DNA damage regulator ATM. Consistent with ATM/ATR involvement, selenite was also shown to stimulate Ser-139 phosphorylation of the ATM/ATR substrate H2AX. Selenite-induced apoptosis was shown to involve DNA topoisomerase II (Top II) as selenite-induced apoptosis was reduced in Top II-deficient HL-60/MX2 cells and in HL-60 cells co-treated with the Top II catalytic inhibitor ICRF-193. Using purified human recombinant Top II, selenite was shown to induce reversible Top II cleavage complexes in vitro. In the aggregate, these results suggest that selenite-induced apoptosis, which involves ATM/ATR and Top II, is likely to be because of DNA damage.

Original languageEnglish
Pages (from-to)29532-29537
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number32
DOIs
Publication statusPublished - Aug 8 2003
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this