Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
Department of Pediatric Hematology and Oncology, Changhua Christian Children's Hospital, Changhua 500, Taiwan.
Phytomedicine. 2019 Feb 15;54:1-8. doi: 10.1016/j.phymed.2018.09.181. Epub 2018 Sep 17.
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.
Celastrol was added to vincristine-resistant cancer cell and immunoreactive proteins were detected.
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.
Celastrol could become a useful agent for treating oral cancers with MDR.
口腔癌是最具侵袭性的恶性肿瘤之一，全球死亡率较高。这些癌症患者采用手术、化疗和放疗相结合的方法进行治疗。
假设/目的：传统中药和其他草药已被用于治疗亚洲的各种疾病。雷公藤红素是从中药雷公藤中分离出的五环三萜类化合物，具有治疗多种疾病的潜力。本研究旨在确定雷公藤红素对长春新碱耐药癌细胞系的影响，并阐明雷公藤红素诱导细胞凋亡的机制。
向长春新碱耐药癌细胞中加入雷公藤红素，并检测免疫反应性蛋白。
我们的研究表明，雷公藤红素通过线粒体和 Fas 介导的途径导致头颈部癌细胞凋亡。然而，这种草药是否对长春新碱耐药的口腔癌患者有有益的影响尚不确定。因此，我们研究了雷公藤红素对长春新碱耐药口腔癌细胞的凋亡作用及其作用机制。本研究表明，雷公藤红素通过内在和外在途径（增加 cleaved caspase-3、caspase-8、caspase-9 和 PARP）诱导细胞周期停滞在 G2/M 期，从而引发细胞凋亡。tBid 表达增加也表明两条途径之间存在串扰。雷公藤红素通过下调 Bcl-2 的表达而不是 Bcl-xL 介导细胞凋亡。此外，JNK1/2 信号通路是雷公藤红素诱导凋亡的主要通路。
雷公藤红素可能成为治疗多药耐药性口腔癌的有用药物。
