Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 391

P08-133 - Flavonoids from Chinese bayberry leaves inhibit ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest via Erk signaling

Monday, Jun 11
8:00 AM – 3:00 PM

Ovarian cancer is one of the leading causes of death related to the female reproductive system in western countries. Patients who experienced platinum based chemotherapy might acquire some side effects and resistance to treatment drugs, which is the major impediment for ovarian cancer treatment. In recent years, natural products have caught great attention in the fight against cancer and flavonoids have been reported to exhibited anti-cancer functions in various signaling pathways. However, studies about the effects of flavonoids on cisplatin-resistant ovarian cancer cells were scarce. Chinese bayberry (Myrica rubra Sieb. et Zucc.) has been cultivated in Southern China for more than 2000 years and is popular among local people. However, leaves from bayberry trees are always abandoned after harvest, which causes huge ecological waste and awaits further utilisation and development. Flavonoids from Chinese bayberry leaves (BLF) contain myricitrin and quercetin 3-rhamnoside as its major components and exhibited strong anti-oxidant property based on the chemical and cellular assays from a previous study from our group. In the present study, we further investigated the effects of BLF on a cisplatin-resistant ovarian cancer cell line A2780/CP70. BLF showed strong inhibitory effects on the growth of A2780/CP70 cells, and such effects might be attributed to the BLF-induced apoptosis and G1 cell cycle arrest. BLF treatment increased the expression of cleaved caspase-3 and -7 and induced apoptosis via a Erk-dependent caspase-9 activation intrinsic apoptotic pathway by up-regulating the pro-apoptotic proteins (Bad and Bax) and down-regulating the anti-apoptotic proteins (Bcl-xL and Bcl-2). Furthermore, by reducing the expression of cyclin D1 and CDK4 and p-Erk, BLF elevated the distribution of G1 phase in cell cycle. BLF exhibited its anti-cancer property by mainly targeting at the Erk pathway, which is quite different from other flavonoids that affect various signaling pathways and might possibly bring about more side effects. Overall, these results indicated that BLF owns the potential to be developed as a valuable source of anti-cancer agent to promote public health.



Funding Source: This research was supported by NIH grants P20RR016477 from the National Center for Research Resources and P20GM103434 from the National Institute for General Medical Sciences (NIGMS) awarded to the West Virginia IDeA Network of Biomedical Research Excellence. This research was supported by Grant Number P20GM104932 from NIGMS, a component of the National Institutes of Health (NIH) and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIGMS or NIH. This study was also supported by COBRE grant GM102488/RR032138, ARIA S10 grant RR020866, FORTESSA S10 grant OD016165 and INBRE grant GM103434. This research was also supported by the National Natural Science Foundation of China (C200501) and the National Key Research and Development Program (2016YFD0400805).
Cell viability

Flow cytometry and staining

Caspases

Intrinsic and Extrinsic

Cell cycle

CoAuthors: Xingqian Ye – Zhejiang University; Yi Charlie Chen – Alderson Broaddus University; Shiguo Chen – Zhejiang University

Yu Zhang

Professor
ZHEJIANG UNIVERSITY
Hangzhou, Zhejiang, China (People's Republic)