Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin-resistant ovarian cancer (A2780) cells.

ABSTRACT

Ovarian cancer is considered as one of the most lethal gynecological cancers, and cisplatin-based therapy has an important role as the first-line option for chemotherapy. Resistance to chemotherapy is the main obstacle against successful cancer chemotherapy with cisplatin. Therefore, identifying potent compositions and molecules with fewer side-effects is a big challenge to overcome cisplatin resistance. In this study, we investigated the possible mechanism and potency of sanguinarine, a plant-derived alkaloid, in human cisplatin-resistant ovarian cancer (A2780/R) cells. The effect of sanguinarine on cytotoxicity of cisplatin was determined by MTT assay. Apoptosis-inducing effect of sanguinarine alone and in combination with cisplatin was evaluated by annexin V/PI assay and DAPI staining. Intracellular glutathione (GSH) content was quantitated using GSH assay kit after treatment with sanguinarine. Results indicated that sanguinarine enhances the sensitivity of A2780/R cells to cisplatin. Apoptosis-inducing effect of cisplatin was also enhanced when combined with sanguinarine. Furthermore, sanguinarine reduced intracellular GSH content in a dose-dependent but not time-dependent manner. These findings suggest that sanguinarine could reverse cisplatin resistance in A2780/R cells through GSH reduction. Therefore, sanguinarine can be used as one of the potent adjuvants for ovarian cancer chemotherapy.