Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Int J Oncol. 2020 Jul;57(1):377-385. doi: 10.3892/ijo.2020.5061. Epub 2020 May 7.
Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported to exhibit anticancer activities in several tumors. The aim of the present study was to investigate the anticancer effects and molecular mechanisms of oridonin in mucoepidermoid carcinoma (MEC). Treatment with oridonin induced the apoptosis of MC‑3 and YD‑15 cell and inhibited the expression of myeloid cell leukemia‑1 (MCL‑1) through the regulation of the protein level through post‑translational regulation in these cell lines. Oridonin significantly increased the expression level of truncated Bid (t‑Bid) as a downstream target of MCL‑1 and subsequently decreased the mitochondrial membrane potential. The ectopic expression of MCL‑1 protein was sufficient to reverse the induction of apoptosis and the increased t‑Bid expression induced by oridonin in both cell lines. Taken together, these results suggest that oridonin exerts an apoptotic effect through the modulation of MCL‑1 and t‑Bid in human MEC cell lines and may thus be a potential anticancer drug candidate for the treatment of human MEC.
冬凌草甲素是从冬凌草中分离得到的一种活性二萜类化合物,据报道其在多种肿瘤中具有抗癌活性。本研究旨在探讨冬凌草甲素在黏液表皮样癌(MEC)中的抗癌作用及其分子机制。冬凌草甲素处理可诱导 MC-3 和 YD-15 细胞凋亡,并通过翻译后调节蛋白水平抑制髓样细胞白血病-1(MCL-1)的表达。冬凌草甲素显著增加了 MCL-1 下游靶蛋白截断 Bid(t-Bid)的表达水平,随后降低了线粒体膜电位。MCL-1 蛋白的异位表达足以逆转冬凌草甲素诱导的两种细胞系中的细胞凋亡和 t-Bid 表达增加。综上所述,这些结果表明,冬凌草甲素通过调节人黏液表皮样癌细胞系中的 MCL-1 和 t-Bid 发挥促凋亡作用,因此可能是治疗人类黏液表皮样癌的潜在抗癌药物候选物。