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Involvement of Both Extrinsic and Intrinsic Apoptotic Pathways in Apoptosis Induced by Genistein in Human Cervical Cancer Cells
Author(s) -
Kim SuHyeon,
Kim SuHyeong,
Lee SangChul,
Song YongSang
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04902.x
Subject(s) - apoptosis , genistein , cervical cancer , cancer research , intrinsic apoptosis , cancer , microbiology and biotechnology , chemistry , medicine , biology , programmed cell death , caspase , biochemistry
Genistein, a naturally occurring isoflavonoid abundant in soy products, has anticancer activity in multiple tumor cells. In this study, we evaluated the apoptotic effect of genistein on cervical cancer cells and its mechanism of apoptosis. Genistein inhibited the proliferation of cervical cancer cells (HeLa, CaSki, and C33A). HeLa cells were the most sensitive to genistein, whereas CaSki and C33A cells were less sensitive. Sub‐G 1 analysis showed that genistein increased apoptotic cells up to 45% at a concentration of 60 μmol/L in HeLa cells, whereas it produced 21% and 17% apoptotic cells in CaSki and C33A cells, respectively, at the same concentration. To determine the apoptotic pathway induced by genistein in the cervical cancer cells, we assessed activation of caspase‐3, ‐8, and ‐9 by immunoblotting. Procaspase‐3, ‐8, and ‐9 were decreased and PARP cleavage increased in a time‐dependent manner after the treatment of genistein in HeLa cells. Also, inhibition of caspase‐3, ‐8, and ‐9 with pharmacological inhibitors reduced genistein‐mediated apoptosis. Interestingly, inhibition of caspase‐8 resulted in remarkable reduction of genistein‐induced apoptosis. Bax expression was increased and total bid decreased, whereas bcl‐2 level was not changed by genistein. Taken together, these results suggest that genistein could induce apoptosis through both extrinsic and intrinsic pathways in human cervical cancer cells.