Dai Xiaoli, Liu Jing, Nian Yin, Qiu Ming-Hua, Luo Ying, Zhang Jihong
Laboratory of Molecular Genetics of Aging and Tumor, Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, P.R. China.
Oncol Rep. 2017 Apr;37(4):2079-2086. doi: 10.3892/or.2017.5444. Epub 2017 Feb 14.
The extract from Cimicifuga, a genus of flowering plants, has been demonstrated to have mainly therapeutic effects on menstrual and menopausal symptoms and also exhibits immunomodulatory, anti-inflammatory and antimicrobial activity. Moreover, the anticancer effects of Cimicifuga have been reported, but the underlying mechanism causing cancer cell death has been poorly described. The present study was designed to investigate the antitumor effects and underlying molecular mechanisms of cimigenol (KY17), a novel cycloartane triterpenoid from Cimicifuga. KY17-induced autophagy and apoptotic cell death in human colon cancer cells (HT-29) was investigated. KY17 treatment induced growth inhibition and apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was confirmed by a change in cell morphology, and an increase in the G2/M phase, as well as increased protein levels of cleaved-caspase-8 and -3; cleavage of poly(ADP-ribose) polymerase (PARP) in the HT-29 cells following KY17 treatment. In addition, autophagy was evaluated by the accumulation of acridine orange, the appearance of green fluorescent protein-light-chain 3 (LC3) punctate structures and increased levels of LC3-II protein expression. Furthermore, combination treatment with the autophagy inhibitor bafilomycin A1 enhanced the induction of apoptosis by KY17. Taken together, the present study provides new insight into the role of KY17 as a potential antitumor compound. Combination of KY17 with an autophagy inhibitor may be a valuable strategy for the chemoprevention or treatment of colon cancer.
升麻属开花植物的提取物已被证明主要对月经和更年期症状有治疗作用，还具有免疫调节、抗炎和抗菌活性。此外，已报道了升麻的抗癌作用，但导致癌细胞死亡的潜在机制描述甚少。本研究旨在探讨升麻新环阿尔廷烷三萜类化合物升麻醇（KY17）的抗肿瘤作用及其潜在分子机制。研究了KY17诱导人结肠癌细胞（HT-29）自噬和凋亡性细胞死亡的情况。KY17处理以浓度依赖的方式诱导生长抑制和凋亡性细胞死亡。细胞形态变化、G2/M期增加以及裂解的半胱天冬酶-8和-3蛋白水平升高，证实了凋亡的诱导；KY17处理后HT-29细胞中聚（ADP-核糖）聚合酶（PARP）的裂解。此外，通过吖啶橙的积累、绿色荧光蛋白轻链3（LC3）点状结构的出现以及LC3-II蛋白表达水平的增加来评估自噬。此外，自噬抑制剂巴弗洛霉素A1联合处理增强了KY17诱导的凋亡。综上所述，本研究为KY17作为潜在抗肿瘤化合物的作用提供了新的见解。KY17与自噬抑制剂联合使用可能是结肠癌化学预防或治疗的一种有价值的策略。
