The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin-3 and stimulating miR-424-3p transcription.

This study investigated if the well-reported anti-tumor effects of resveratrol (RES) is mediated by modulation levels of galectin-3 (GAL-3), an anti-apoptotic lectin that is highly overexpressed in ovarian cancer cells. SKOV3 and OVCAR-3 OC cells were untreated or incubated with DMOS or increasing concentrations of RES (25, 50, 100 μM) for 72 hr. RES, in a dose-dependent manner and in both cell lines, induced cell death and inhibited cell migration and invasion It also downregulated Bcl-2 levels, increased cleaved caspase-3, and GAL-3 protein (but not mRNA) levels, suggesting increased breakdown. These effects were associated with reduced levels of p-NF-κB P65, p-IKKα/β, and p-Akt, major targets of Gal-3. Further investigation showed that RES enhanced levels of miR-424-3p which is able to degrade GAL-3. Conclusion: Findings of this study suggest that RES induced apoptosis in cancerous cells is associated with increased levels of miR-424-3p and reduced levels of GAL-3. PRACTICAL APPLICATIONS: This study highlights a possible mechanism by which RES could enhance cell death in OC cells and enhances their sensitivity to cisplatin. RES apoptotic effect and enhancement of OC cells to chemotherapy were associated with decreased abundance of GAL-3, a common cell survival molecule that promotes tumorigenesis and increased transcription of miR-424-3p that has the ability to degrade cellular GAL-3. These findings add a possible new mechanism by which RES acts and opens a window for further research to understand its mechanism of action.