Flavonoids from Chinese bayberry leaves induced apoptosis and G1 cell cycle arrest via Erk pathway in ovarian cancer cells

• Published in: European journal of medicinal chemistry Vol. 147; pp. 218 - 226
• Main Authors: Zhang, Yu, Chen, Shiguo, Wei, Chaoyang, Rankin, Gary O., Ye, Xingqian, Chen, Yi Charlie
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 10.03.2018
• Subjects: Apoptosis; Apoptosis - drug effects; Cell Cycle - drug effects; Cell cycle arrest; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; ERK; Female; Flavonids; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; G1 Phase Cell Cycle Checkpoints - drug effects; Humans; MAP Kinase Signaling System - drug effects; Molecular Structure; Myrica - chemistry; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Plant Leaves - chemistry; Structure-Activity Relationship; Tumor Cells, Cultured; Cell cycle arrest; Flavonids; Apoptosis; ERK; Ovarian cancer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.01.084

Ovarian cancer is one of the leading causes of death related to the female reproductive system in western countries. Adverse side effects and resistance to platinum based chemotherapy have become the major obstacles for ovarian cancer treatment. Natural products have gained great attention in cancer treatment in recent years. Chinese bayberry leaves flavonoids (BLF) containing rich content of myricitrin (myricetin 3-O-rhamnoside) and a part of quercetrin (quercetin 3-rhamnoside) inhibited the growth of an ovarian cancer cell line A2780/CP70. Such inhibitory effects might be due to the induction of 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), which were also in consistency with the results from Hoechst 33342 staining and flow cytometry analysis. Furthermore, by reducing the expression of cyclin D1 and CDK4 and p-Erk, BLF elevated the distribution of G1 phase in cell cycle and thus caused G1 cell cycle arrest. Overall, these results indicated that BLPs could be a valuable resource of natural compound for ovarian cancer treatment. [Display omitted] •BLF inhibited cell viability of cisplatin-resistant ovarian cancer A2780/CP70 cells.•Flow cytometry analysis showed that BLF induced apoptosis in A2780/CP70 cells.•BLF activated caspase-3 and caspase-7 to induce apoptosis in A2780/CP70 cells.•BLF induced apoptosis via the Erk-induced intrinsic apoptotic pathway.•BLF induced G1 cell cycle arrest in A2780/CP70 cells.