| Title | Involvement of both extrinsic and intrinsic apoptotic pathways in apoptosis induced by genistein in human cervical cancer cells. | | Author(s) | Kim SH, Kim SH, Lee SC, Song YS | | Institution | Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. | | Source | Ann N Y Acad Sci 2009 Aug.:196-201. | | MeSH | Apoptosis
BH3 Interacting Domain Death Agonist Protein
Blotting, Western
Caspase 3
Caspase 8
Caspase 9
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cysteine Proteinase Inhibitors
Dose-Response Relationship, Drug
Female
Flow Cytometry
Genistein
Hela Cells
Humans
Oligopeptides
Proto-Oncogene Proteins c-bcl-2
Signal Transduction
Time Factors
Uterine Cervical Neoplasms
bcl-2-Associated X Protein
| | Abstract | 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 micromol/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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19723056 |
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