Celastrol induces vincristine multidrug resistance oral cancer cell apoptosis by targeting JNK1/2 signaling pathway.
Phytomedicine. 2019 Feb 15 ;54:1-8. Epub 2018 Sep 17. PMID: 30668359
BACKGROUND: Oral 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/PURPOSE: Traditional 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 DESIGN: Celastrol was added to vincristine-resistant cancer cell and immunoreactive proteins were detected.
METHODS AND RESULTS: Our 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.
CONCLUSION: Celastrol could become a useful agent for treating oral cancers with MDR.