Azidothymidine induces apoptosis in mouse myeloma cell line Sp2/0.
Azidothymidine (AZT), which has been extensively used as an antiviral agent in the treatment of AIDS, showed strong inhibition of growth of Sp2/0 cells in vitro. AZT-treated cells showed a decrease in viability in a dose-dependent manner. AZT specifically induced typical apoptotic cell death with DNA double-strand cleavage and subsequent formation of apoptotic bodies. The induction of DNA double-strand cleavage into the oligonucleosomal ladder by AZT was protected in the presence of thymidine or uridine. An increase in endonuclease activity from nuclear extract of AZT-treated cells was observed. The enzyme activity was found to be Ca(2+)-and Mg(2+)-dependent and was inhibited by zinc acetate. A marked enhancement of PARP activity was observed in AZT-treated cells. These observations show that AZT can trigger both morphological and biochemical changes typical of apoptosis in the mouse myeloma cell line Sp2/0.
Sailaja
G
G
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Nayak
R
R
Antony
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine; D004247:DNA