Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Phytomedicine. 2012 Jun 15;19(8-9):756-62. doi: 10.1016/j.phymed.2012.02.014. Epub 2012 Mar 29.
Triptolide, a diterpene triepoxide compound extracted from the traditional Chinese medicine herb Tripterygium wilfordii Hook F., is a potential cancer chemotherapeutic for tumors. However, the mechanism of anti-proliferative mechanism of triptolide in colon cancer cells is not entirely clear. Triptolide markedly inhibited HT29 and SW480 cells proliferation in a dose- and time-dependent manner. Triptolide decreased ERK and AKT phosphorylation, and GABPα expression in colon cancer cells. Beta-catenin expression and phosphorylation were not altered by incubation of triptolide. However, we found that triptolide repressed expression of LEF/TCF. Although it did not significantly affect cells apoptosis, triptolide induced G1 phase arrest dose-dependently. Further detection for the expression of cell cycle-related proteins suggesting that triptolide stimulate expression of p21 and repress cyclin A1. Increased p21 binded to CDK4/CDK6, therefore blocked function of CDK4/CDK6, and subsequently contribute to the G1 arrest. These data suggested that triptolide is a potential agent for treatment of colon cancer, and its anti-proliferation effect mainly occur through G1 phase arrest.
雷公藤红素是从传统中药雷公藤中提取的二萜三环氧化合物，是一种有潜力的肿瘤化疗药物。然而，雷公藤红素在结肠癌细胞中的抗增殖机制尚不完全清楚。雷公藤红素以剂量和时间依赖的方式显著抑制 HT29 和 SW480 细胞的增殖。雷公藤红素降低了结肠癌细胞中 ERK 和 AKT 的磷酸化和 GABPα 的表达。β-连环蛋白的表达和磷酸化不受雷公藤红素孵育的影响。然而，我们发现雷公藤红素抑制了 LEF/TCF 的表达。尽管它对细胞凋亡没有显著影响，但雷公藤红素剂量依赖性地诱导 G1 期阻滞。进一步检测细胞周期相关蛋白的表达表明，雷公藤红素刺激 p21 的表达并抑制 cyclin A1。增加的 p21 与 CDK4/CDK6 结合，从而阻断 CDK4/CDK6 的功能，随后导致 G1 期阻滞。这些数据表明，雷公藤红素是治疗结肠癌的潜在药物，其抗增殖作用主要通过 G1 期阻滞发生。
