RESUMO
Ovarian cancer (OC) is among the top gynecologic cancers in the US with a death tally of 13,940 in the past year alone. Gallic acid (GA) is a natural compound with pharmacological benefits. In this research, the role of GA on cell proliferation, cell apoptosis, cell cycle-related protein expression was explored in OC cell lines OVCAR-3 and A2780/CP70. After 24,48 and 72 h of GA treatment, the IC50 values in OVCAR-3 cells were 22.14 ± 0.45, 20.36 ± 0.18, 15.13 ± 0.53 µM, respectively and in A2780/CP70 cells IC50 values were 33.53 ± 2.64, 27.18 ± 0.22, 22.81 ± 0.56, respectively. Hoechst 33,342 DNA staining and flow cytometry results showed 20 µM GA exposure could significantly accelerate apoptosis in both OC cell lines and the total apoptotic rate increased from 5.34%(control) to 21.42% in OVCAR-3 cells and from 8.01%(control) to 17.69% in A2780/CP70 cells. Western blot analysis revealed that GA stimulated programmed OC cell death via a p53-dependent intrinsic signaling. In addition, GA arrested cell cycle at the S or G2 phase via p53-p21-Cdc2-cyclin B pathway in the same cells. In conclusion, we provide some evidence of the efficacy of GA in ovarian cancer prevention and therapy.
RESUMO
Ovarian cancer is the second most common gynecologic cancer with an estimated 13,940 mortalities across the United States in 2020. Natural polyphenols have been shown to double the survival time of some cancer patients due to their anticancer properties. Therefore, the effect of polyphenols extracted from Chinese hickory seed skin Carya cathayensis (CHSP) on ovarian cancer was investigated in the present study. Cell viability results showed that CHSP is more effective in inhibiting ovarian cancer cells than normal ovarian cells, with the IC50 value for inhibition of cell proliferation of Ovarian cancer cells (OVCAR-3) being 10.33 ± 0.166 µg/mL for a 24 h treatment. Flow cytometry results showed that the apoptosis rate was significantly increased to 44.21% after 24 h treatment with 20 µg/mL of CHSP. Western blot analysis showed that CHSP induced apoptosis of ovarian cancer cells through a p53-dependent intrinsic pathway. Compared with control values, levels of VEGF excreted by OVCAR-3 cancer cells were reduced to 7.87% with a 40 µg/mL CHSP treatment. Consistent with our previous reports, CHSP inhibits vascular endothelial growth factor (VEGF) secretion by regulating the HIF-1α-VEGF pathway. In addition, we also found that the inhibitory effect of CHSP on ovarian cancer is related to the up-regulation of Phosphatase and tension homolog (PTEN) and down-regulation of nuclear factor kappa-B (NF-kappa B). These findings provide some evidence of the anti-ovarian cancer properties of CHSP and support the polyphenols as potential candidates for ovarian cancer adjuvant therapy.