Abstract
The purpose of this study is to investigate whether and how kaempferol, a dietary flavonoid, induces apoptosis in human ovarian cancer cells.
Ovarian cancer cell lines, OVCAR-3, A2780/CP70, and A2780/wt, were treated with kaempferol for 24 hours and analyzed for cell proliferation and cytotoxicity by genomic DNA staining and LDH assay, respectively. Apoptosis of cells were detected with Caspase-Glo 3/7 Assay. Intrinsic apoptotic pathway was further confirmed by pre-treating cancer cells with caspase-9 inhibitor, and tested for caspase 3/7 levels after kaempferol treatment. Protein levels of pro-apoptosis genes including p53, Bad, and Bax, and anti-apoptosis gene, Bcl-XL, were analyzed by western blots.
Our data demonstrate that kaempferol inhibits cell proliferation but causes no necrosis in all 3 ovarian cancer cell lines. For apoptosis, caspase 3/7 levels were escalated by kaempferol treatment concentration-dependently and significantly. This effect can be diminished by pre-treatment with caspase-9 inhibitor, indicating an intrinsic apoptosis pathway involved in kaempferol-induced apoptosis in ovarian cancer cells. Western blot analysis revealed that protein levels of anti-apoptosis gene, Bcl-xL were decreased in ovarian cancer cells, while pro-apoptotic genes, p53, Bad, and Bax, were up-regulated by kaempferol treatment.
In conclusion, kaempferol induces apoptosis in ovarian cancer cells through regulating expression of both pro-apoptotic and anti-apoptotic genes within the intrinsic apoptosis pathway. As a natural flavonoid wildly distributed in fruits and vegetables, kaempferol is a good candidate for chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 189. doi:10.1158/1538-7445.AM2011-189