Effects of Curcumin and Its Analogue Desmethoxycurcumin on miR-133b and Its Target Gene GSTP-1 in Cisplatin-resistant Ovarian Cancer Cells

Abstract

Background/Aim: Ovarian cancer, despite being the fifth most common gynecological malignancy, has the highest mortality rate. Recent clinical studies have explored the potential of natural products, like curcumin (CUR), to enhance conventional chemotherapy by targeting multiple cellular pathways. This study aimed to evaluate the effects of CUR and its analog, demethoxycurcumin (DMC), on human ovarian cancer and cisplatin-resistant ovarian cancer cell proliferation and apoptosis. Additionally, we investigated the expression of a candidate gene (GSTP-1), and microRNA (miR-133b) involvement in glutathione metabolism, a potential resistance mechanism in cisplatin-resistant ovarian cancer cells. Materials and Methods: Cell proliferation was measured using the WST-1 assay after exposing cisplatin-resistant (A2780cp) and sensitive (A2780) ovarian cancer cell lines to various concentrations of CUR and DMC for different time periods. Apoptosis was quantified using the Annexin V-FITC/PI assay. To understand the underlying mechanisms, we examined the expression levels of GSTP-1 and miR-133b using quantitative RT-PCR. Results: The WST-1 assay revealed that CUR and DMC inhibited cell proliferation in both cell lines, with cisplatin causing a sharper viability decline in A2780cp cells. Annexin V-PI staining detected early apoptosis induced by CUR, DMC, and their combinations in both cell lines at 12 hours, with no necrosis observed. Gene expression analysis showed a significant decrease in GSTP-1 and miR-133b levels in A2780cp cells compared to A2780 cells. The combination treatments, particularly Cur+DMC+Cisplatin, synergistically reduced GSTP-1 and miR-133b expression. Conclusion: This study demonstrated the potential of CUR and DMC to enhance the efficacy of cisplatin in ovarian cancer treatment. The observed decrease in GSTP-1 and miR-133b expression in cisplatin-resistant cells suggests their involvement in drug resistance and highlights their potential as therapeutic targets.