Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin-resistant ovarian cancer (A2780) cells.
Chem Biol Drug Des
; 95(2): 215-223, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31512406
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Cisplatino
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Resistencia a Medicamentos Antineoplásicos
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Benzofenantridinas
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Glutationa
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Isoquinolinas
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article