Prodelphinidins isolated from Chinese bayberry leaves induces apoptosis via the p53-dependent signaling pathways in OVCAR-3 human ovarian cancer cells

Abstract

Abstract. 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.

Orostachys japonicus induce p53‐dependent cell cycle arrest through the MAPK signaling pathway in OVCAR‐3 human ovarian cancer cells

“…To evaluate the general effect of apoptosis, cells were stained with Annexin V‐FITC and PI, and then the cell population stages were analyzed using flow cytometry. The early or late apoptotic cells were classified as quadrants, which are presented in the lower‐right (Annexin V + /PI − ) and upper‐right (Annexin V + /PI + ) quadrants (Fu, Ye, Lee, Rankin, & Chen, 2017). OJE significantly induced the early and late apoptosis stages in a concentration‐dependent manner (Figure 3a).…”

“…Therefore, OJE can effectively induce OVCAR-3 cancer cell death, even at half the concentrations of those observed in previous studies Figure 1. (Fu, Ye, Lee, Rankin, & Chen, 2017). OJE significantly induced the early and late apoptosis stages in a concentration-dependent manner (Figure 3a).…”

Polyphenols Extracted from Chinese Hickory (Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells

“…Our previous work reported that polyphenols, prodelphinidins [ 25 ], theaflavin-3′-gallate [ 26 ] and galangin [ 27 ], induced apoptosis in ovarian cancer cells through the activation of p53 protein. To determine whether p53 is involved in CHSP-induced apoptosis of ovarian cancer cells, the expression of p53 protein was detected by Western blot.…”

Inhibition of NET‑1 suppresses proliferation and promotes apoptosis of hepatocellular carcinoma cells by activating the PI3K/AKT signaling pathway

“…During programmed cell death, activation of caspase-3 leads to proteolysis of DNA repair proteins and cytoskeletal proteins to alter the morphology and DNA of cells (45). Dysregulation of caspase-3 was reported in several malignancies (46)(47)(48) and overexpression of this protein was reported in HCC (49).…”