Se-methylselenocysteine induces apoptosis through caspase activation in HL-60 cells

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Apoptosis, a programmed process of cell suicide, has been proposed as the most plausible mechanism for the chemopreventive activities of selenocompounds, In our study, we found that Se-methylselenocysteine (MSG) induced apoptosis through caspase activation in human promyelocytic leukemia (HL-60) cells. Measurements of cytotoxicity, DNA fragmentation and apoptotic morphology revealed that MSC was more efficient at inducing apoptosis than selenite, but was less toxic. Moreover, MSG increased both the apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activity, whereas selenite did not. We next examined whether caspases and serine proteases are required for the apoptotic induction by MSG. A general caspase inhibitor, z-VAD-fmk, dramatically decreased cytotoxicity in MSG-treated HL-60 cells and several other apoptotic features, such as, caspase-3 activation, the apoptotic DNA ladder, TUNEL-positive staining and the DNA double-strand break. Interestingly, a general serine protease inhibitor, AAPV-cmk, also effectively inhibited MSG-mediated cytotoxicity and apoptosis, These results demonstrate that MSC is a selenocompound that efficiently induces apoptosis in leukemia cells and that proteolytic machinery, in particular caspase-3, is necessary for MSC-induced apoptosis, On the other hand, selenite-induced cell death could be derived from necrosis rather than apoptosis, since selenite did not significantly induce several apoptotic phenomena, including the activation of caspase-3.
Publisher
OXFORD UNIV PRESS
Issue Date
2001-04
Language
English
Article Type
Article
Keywords

MAMMARY-CANCER CHEMOPREVENTION; EPITHELIAL TUMOR-CELLS; IN-VITRO; SELENIUM-COMPOUNDS; LEUKEMIA-CELLS; STRAND BREAKS; DNA; INDUCTION; INHIBITION; PROTEASE

Citation

CARCINOGENESIS, v.22, no.4, pp.559 - 565

ISSN
0143-3334
DOI
10.1093/carcin/22.4.559
URI
http://hdl.handle.net/10203/79434
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