Celastrol induces vincristine multidrug resistance oral cancer cell apoptosis by targeting JNK1/2 signaling pathway

Abstract

BackgroundOral cancers are one of the most aggressive malignancies, with high mortality rates globally. Patients with these cancers are treated using combination therapies including surgery, chemotherapy, and radiotherapy. Hypothesis/PurposeTraditional Chinese medicines and other herbal medicines have been used to treat various diseases in Asia. Celastrol is a pentacyclic triterpenoid isolated from the Chinese herbal medicine Trypterygium wilfordii, which has therapeutic potential in multiple diseases. The present study was to determine the effect of celastrol on vincristine-resistant cancer cell line and to illuminate the mechanism of celastrol-induced cell apoptosis. Study DesignCelastrol was added to vincristine-resistant cancer cell and immunoreactive proteins were detected. Methods and ResultsOur study demonstrated that celastrol leads to apoptosis of head and neck cancer cells through mitochondria- and Fas-mediated pathways. However, whether this herbal medicine exhibits beneficial effects on vincristine-resistant oral cancer patients remains uncertain. Therefore, our study examined the apoptotic effect exerted by celastrol and the mechanism by this drug acts on a vincristine-resistant cancer cell line. The present study demonstrated that celastrol triggered apoptotic cell death by inducing cell cycle arrest at the G2/M phase via the intrinsic and extrinsic pathways (increased cleaved caspase-3, caspase-8, caspase-9, and PARP). Increased expression of tBid also indicated the presence of crosstalk between the two pathways. Celastrol mediated cell apoptosis through the downregulation of the expression of Bcl-2, not Bcl-xL. Moreover, JNK1/2 signaling was the main pathway of celastrol-induced apoptosis. ConclusionCelastrol could become a useful agent for treating oral cancers with MDR.