DNA Damage-mediated Apoptosis Induced by Selenium Compounds

• DOI: 10.1074/jbc.m301877200
• Publication Date: 2003-08-01T20:08:49Z
• Authors: Nai Zhou; Hai Xiao; Tsai-Kun Li; Alam Nur-E-Kamal; Leroy F. Liu
• Keywords: 0301 basic medicine; Dose-Response Relationship, Drug; Immunoblotting; Apoptosis; HL-60 Cells; 3T3 Cells; DNA Fragmentation; Diketopiperazines; Glutathione; Piperazines; Recombinant Proteins; Histones; Mice; Selenium; 03 medical and health sciences; Animals; Humans; Comet Assay; Phosphorylation; Poly(ADP-ribose) Polymerases; RNA, Small Interfering; DNA Damage

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