PMID- 28529565 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 13 IP - 5 DP - 2017 May TI - Prodelphinidins isolated from Chinese bayberry leaves induces apoptosis via the p53-dependent signaling pathways in OVCAR-3 human ovarian cancer cells. PG - 3210-3218 LID - 10.3892/ol.2017.5813 [doi] AB - Chinese bayberry leaves are rich in prodelphinidins. Since the isolation and purification of prodelphinidins is difficult, the association between the degree of prodelphinidin polymerization and their anti-carcinogenic activity remains ambiguous. The cytotoxic and apoptotic activities of prodelphinidin Chinese bayberry leaf extracts (PCBLs), oligomeric proanthocyanidins (OPAs) and polymeric proanthocyanidins (PPAs), isolated by normal-phase preparative high-performance liquid chromatography were investigated in OVCAR-3 human ovarian cancer cells. The PCBLs, OPAs and PPAs inhibited cancer cell growth and induced apoptosis via the caspase-dependent pathway. Apoptosis was triggered through the intrinsic pathway by upregulating the expression of several B-cell lymphoma-2 (Bcl-2) family proapoptotic proteins, including p53-upregulated modulator of apoptosis (PUMA), Bcl-2-associated X protein and Bcl-2-associated agonist of cell death, and by downregulating the antiapoptotic protein Bcl-extra large. Apoptosis was also triggered through the extrinsic pathway via the upregulation of death receptor 5 (DR5) and Fas expression. In addition, OPAs and PPAs induced caspase-dependent apoptosis at least partially through the inhibition of the protein kinase B signaling pathway. The knockdown of p53 by specific small interfering RNA resulted in the depletion of p53, and inhibited the OPA and PPA treatment-induced increases in p53, which led to a decrease in the expression of p21, DR5, Fas, PUMA and phosphatase and tensin homolog proteins. These observations demonstrate that p53 is a mediator of OPA and PPA-induced apoptosis in OVCAR-3 cells. The PPAs exhibited stronger anti-proliferative and pro-apoptotic activities compared with OPAs and PCBLs. These results suggest that PCBLs, OPAs and PPAs may be useful for the treatment of ovarian cancer. FAU - Fu, Yu AU - Fu Y AD - College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China. AD - College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA. FAU - Ye, Xingqian AU - Ye X AD - College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China. FAU - Lee, Malcolm AU - Lee M AD - College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA. FAU - Rankin, Gary AU - Rankin G AD - Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA. FAU - Chen, Yi Charlie AU - Chen YC AD - College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA. LA - eng PT - Journal Article DEP - 20170306 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5431737 OTO - NOTNLM OT - Myrica rubra OT - apoptosis OT - leaves OT - ovarian cancer OT - prodelphinidins EDAT- 2017/05/23 06:00 MHDA- 2017/05/23 06:01 PMCR- 2017/03/06 CRDT- 2017/05/23 06:00 PHST- 2016/04/27 00:00 [received] PHST- 2016/12/02 00:00 [accepted] PHST- 2017/05/23 06:00 [entrez] PHST- 2017/05/23 06:00 [pubmed] PHST- 2017/05/23 06:01 [medline] PHST- 2017/03/06 00:00 [pmc-release] AID - OL-0-0-5813 [pii] AID - 10.3892/ol.2017.5813 [doi] PST - ppublish SO - Oncol Lett. 2017 May;13(5):3210-3218. doi: 10.3892/ol.2017.5813. Epub 2017 Mar 6.