Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9

Abstract

Ovarian cancer is the third most common cancer in the female reproductive organs and epithelial ovarian cancer has the highest lethality of all gynecological cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of several types of cancer other than ovarian cancer. In this study, we exposed the ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and luteolin). MTT and wound healing assays demonstrated that all three treatments suppressed the proliferation and migration of the ovarian cancer cells. In addition, western blotting and ELISA assays showed that the expression levels of MMP2 and MMP9 gradually decreased after treatment with increasing concentrations of ellagic acid and luteolin. To confirm our findings in the in vitro experiments, we used another ovarian cancer cell line, ES-2, in nude mice experiments. All three treatments inhibited tumor growth without obvious side-effects. Furthermore, compared with the control group, the expression levels of MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a promising candidate for further preclinical testing for treatment of human ovarian cancer.