Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway

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.