title: Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway.
abstract: Ovarian cancer is a significant malignancy for women in the western world, and its death rate has remained unchanged over the past 50 years, leaving room for proper chemoprevention. Kaempferol is a natural flavonoid widely distributed in fruits and vegetables, and epidemiological studies have found a negative correlation between kaempferol consumption and ovarian cancer risk. To understand the mechanism behind this negative correlation, we investigated kaempferol's ability to induce apoptosis in A2780/CP70, A2780/wt, and OVCAR-3 ovarian cancer cell lines. Kaempferol inhibited cell proliferation but did not cause necrosis in all 3 cell lines. For the apoptosis, caspase 3/7 levels were induced in a concentration-dependent manner by kaempferol treatment, with A2780/wt cells being the most responsive. This induction can be diminished by pre-treatment with a caspase-9 inhibitor, indicating an intrinsic apoptosis pathway. Western blot analysis revealed that protein levels of Bcl-x(L) were decreased in ovarian cancer cells, while p53, Bad, and Bax proteins were up-regulated by kaempferol treatment. Our data indicate that kaempferol induces apoptosis in ovarian cancer cells through regulating pro-apoptotic and anti-apoptotic protein expressions in the intrinsic apoptosis pathways, and is a good candidate for the chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are therefore warranted.
authors.affiliation: Natural Science Division, Alderson-Broaddus College, Philippi, WV.
authors.forename: Haitao
authors.initials: H
authors.lastname: Luo
authors.forename: Gary O
authors.initials: GO
authors.lastname: Rankin
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Li
authors.forename: Laura
authors.initials: L
authors.lastname: Depriest
authors.forename: Yi Charlie
authors.initials: YC
authors.lastname: Chen