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

• Published in: Anti-cancer agents in medicinal chemistry Vol. 17; no. 11; p. 1519
• Main Authors: Cho, Eugene, Chung, Eun Y, Jang, Hye-Yeon, Hong, On-Yu, Chae, Hee S, Jeong, Young-Ju, Kim, Sun-Young, Kim, Byeong-Soo, Yoo, Dong J, Kim, Jong-Suk, Park, Kwang-Hyun
• Format: Journal Article
• Language: English
• Published: Netherlands 24-11-2017
• Subjects: Animals; Anthocyanins - chemistry; Anthocyanins - metabolism; Anthocyanins - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Caspase 3 - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Glucosides - chemistry; Glucosides - metabolism; Glucosides - pharmacology; Humans; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred ICR; Molecular Structure; Morus - chemistry; Structure-Activity Relationship; Tumor Cells, Cultured; Cyanidin-3-glucoside; DNA fragmentation; nude mice; mulberry; anti-cancer; Morus alba L; caspase-3
• DOI: 10.2174/1871520617666170327152026
• EISSN: 1875-5992

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.
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 by 1H and 13C 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.
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.
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.