Therapeutic Effects of Punicalagin Against Ovarian Carcinoma Cells in Association With β-Catenin Signaling Inhibition

Aim: The aimof this studywas to investigate the effects of punicalagin, a polyphenol isolated from Punica granatum, on human A2780 ovarian cancer cells in vitro. Methods: The viability of human A2780 ovarian cells was evaluated using Cell Counting Kit-8 assay. Cell cycle was detected with flow cytometry analysis. The protein expression levels of Bcl-2, Bax, beta-catenin, cyclin D1, survivin, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-3 were measured usingWestern blot analysis. Matrix metalloproteinase (MMP)-2 andMMP-9 activitywas determinedwith gelatin zymography. Wound healing assay was used to determine cell migration. Results: Punicalagin inhibited the cell viability of A2780 cells in a dose-and time-dependent manner, and the cell cycle of A2780 cells was arrested in G1/S phase transition. The treatment also induced apoptosis as shown by the up-regulation of Bax and down-regulation of Bcl-2. On the other hand, punicalagin treatment increased the expressions of TIMP-2 and TIMP-3, decreased the activities of MMP-2 and MMP-9, and inhibited cell migration. In addition, the beta-catenin pathway was suppressed as shown by the down-regulations of beta-catenin and its downstream factors including cyclin D1 and survivin. Conclusions: Punicalagin may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against human ovarian cancer in humans through the inhibition of beta-catenin signaling pathway.