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J Funct Foods. 2018 Jan;40:573-581. doi: 10.1016/j.jff.2017.11.045. Epub 2017 Dec 22.

Dietary Compound Proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves inhibit angiogenesis and regulate cell cycle of cisplatin-resistant ovarian cancer cells via targeting Akt pathway.

Author information

1
Zhejiang University, Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, Zhejiang R & D Center for Food Technology and Equipment, Hangzhou 310058, China.
2
College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV, 26416, USA.
3
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
4
Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, 26506, USA.
5
Department of Tea Science, Zhejiang University, Hangzhou 310058, China.

Abstract

Ovarian cancer is the leading cause of death from gynecological malignancy and natural products have drawn great attention for cancer treatment. Chinese bayberry leaves proanthocyanidin (BLPs) with epigallocatechin-3-O-gallate (EGCG) as its terminal and major extension units is unusual in the plant kingdom. In the present study, BLPs showed strong growth inhibitory effects on cisplatin-resistant A2780/CP70 cells by inhibiting angiogenesis and inducing G1 cell cycle arrest. BLPs reduced the tube formation in HUVECs and attenuated the wound healing ability in A2780/CP70 cells. BLPs further reduced the level of ROS and targeted Akt/mTOR/p70S6K/4E-BP-1 pathway to reduce the expression of HIF-1α and VEGF, and thus inhibited angiogenesis. Furthermore, BLPs induced G1 cell cycle arrest by reducing the expressions of c-Myc, cyclin D1 and CDK4, which was also in accordance with the flow cytometry analysis. Overall, these results indicated that BLPs could be a valuable resource of natural compounds for cancer treatment.

KEYWORDS:

Akt; Chinese bayberry leaves; Proanthocyanidins; angiogenesis; cell cycle; ovarian cancer

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