Nitidine chloride inhibits proliferation and induces apoptosis in ovarian cancer cells by activating the Fas signalling pathway

Abstract

Objectives: To explore the apoptotic effects and underlying mechanisms of nitidine chloride (NC) in epithelial ovarian cancer.

Methods: The MTT cell proliferation assay was used to detect the inhibitory effects of different concentrations of NC (0, 0.3125, 0.625, 1.25, 2.5, 5 and 10 μg/ml) in SKOV3 ovarian carcinoma cells. The number of apoptotic cells was observed by Hoechst staining and measured by flow cytometry. Quantitative PCR was used to measure the expression of Fas, Fas-associated death domain-containing protein (FADD), caspase-8 and caspase-3. RNA interference (RNAi) was used to determine whether caspase-8 played an important role in NC-induced apoptosis.

Key findings: Nitidine chloride inhibited the proliferation of SKOV3 cells (IC₅₀ = 2.317 ± 0.155 μg/ml) after 24 h of treatment and induced apoptosis (15.9-64.3%). Compared with the control group, a significant increase in Fas, FADD, caspase-8 and caspase-3 gene expression was observed in the NC-treated groups (P < 0.05). After silencing caspase-8 by RNAi, the antiproliferative activity and pro-apoptotic activity of NC in SKOV3 cells decreased (P < 0.05).

Conclusions: Our study showed that NC induced apoptosis in SKOV3 cells by activating the Fas signalling pathway, and caspase-8 played an important role in this process.

Keywords: Fas signalling pathway; apoptosis; nitidine chloride; ovarian cancer.