Celastrol, a plant-derived triterpene, induces cisplatin-resistance nasopharyngeal carcinoma cancer cell apoptosis though ERK1/2 and p38 MAPK signaling pathway

Abstract

BackgroundDeveloping resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace. Hypothesis/PurposeThe present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells. ResultsStudy results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2. ConclusionTaken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.