Anti-cancer Effect of Cyanidin-3-glucoside from Mulberry via Caspase-3 Cleavage and DNA Fragmentation in vitro and in vivo

Background: Fruits of Morus alba L. (mulberry) have various bioactive compounds such as polyphenols and anthocyanins and used as a herbal medicine. However, the anti-cancer effects and molecular basis have not been elucidated. Methods: We isolated the cyanidin-3-glucoside in various cultivar of mulberry by acidified-methanol extraction methods. This molecule were compared mass spectroscopic properties by LC-MS/MS and analyzed by¹H and¹³C NMR. We examined the anti-cancer effect with molecular mechanisms of the cyanidin-3-glucoside on MDA-MB-453 human breast cancer cells and xenograft animal model. Results: The treatment with the mulberry cyanidin-3-glucoside decreased cell viability in a dose-dependent manner with alteration of apoptotic protein contents, and DNA fragmentation, suggesting that cells undergo apoptosis. Supporting the observations, Treatment with the cyanidin-3-glucoside showed active apoptosis by caspase-3 cleavage and DNA fragmentation through Bcl-2 and Bax pathway. Indeed, cyanidin-3-glucoside inhibits tumor growth in MDA-MB-453 cells-inoculated nude mice. Tumor growth of xenograft nude mouse was significantly reduced compared to the control group by the cyanidin-3-glucoside. Conclusion: The data demonstrate that cyanidin-3-glucoside isolated from mulberry induced apoptosis in breast cancer (MDA-MB-453) cells, and therefore, has a potential as an anti-cancer agent. These results show that mulberry cyanidin-3-glucoside inhibit the proliferation and growth in vitro and in vivo model and, indicating the inhibition of tumor progression.