1. Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin-resistant ovarian cancer (A2780) cells.
- Author
-
Sarkhosh-Inanlou R, Molaparast M, Mohammadzadeh A, and Shafiei-Irannejad V
- Subjects
- Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Drug Synergism, Female, Humans, Ovarian Neoplasms metabolism, Antineoplastic Agents pharmacology, Benzophenanthridines pharmacology, Cisplatin pharmacology, Drug Resistance, Neoplasm drug effects, Glutathione metabolism, Isoquinolines pharmacology, Ovarian Neoplasms pathology
- 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., (© 2019 John Wiley & Sons A/S.)
- Published
- 2020
- Full Text
- View/download PDF