Zhang Bin, Wang Zhong-Feng, Tang Mian-Zhi, Shi Yu-Liang
Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031 P. R. China.
Invest New Drugs. 2005 Dec;23(6):547-53. doi: 10.1007/s10637-005-0909-5.
Toosendanin, a triterpenoid derivative isolated from the barks of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris for more than fifty years in China. In the present study, we investigated the growth inhibition and apoptosis-induced effect of toosendanin on human cancer cells. The result showed that toosendanin significantly suppressed the proliferation of tested human cancer cell lines. The IC(50) values were less than 1.7 x 10(-7) M and U937 was the most sensitive cell line with a IC(50) of 5.4 x 10(-9) M. Flow cytometric analysis revealed that treatment of U937 cells with toosendanin resulted in a dose- and time-dependent accumulation of cells in the S phase with a concomitant decrease in cells processing to G(0)/G(1) phase. The growth inhibition of U937 cells after exposure to toosendanin was subsequently associated with the induction of apoptosis, as evidence by the typical condensed and fragmented nuclei, DNA fragmentation, and exposure of phosphatidylserine on the outer leaflet of plasma membrane. All these results indicated that toosendanin could serve as a potential candidate for anticancer drug.
川楝素是从川楝（Melia toosendan Sieb et Zucc）树皮中分离得到的一种三萜类衍生物，在中国作为驱蛔虫的驱虫药已使用了五十多年。在本研究中，我们研究了川楝素对人癌细胞的生长抑制和诱导凋亡作用。结果表明，川楝素显著抑制了受试人癌细胞系的增殖。半数抑制浓度（IC50）值小于1.7×10−7 M，U937是最敏感的细胞系，IC50为5.4×10−9 M。流式细胞术分析显示，用川楝素处理U937细胞导致S期细胞呈剂量和时间依赖性积累，同时进入G0/G1期的细胞减少。川楝素处理后U937细胞的生长抑制随后与凋亡诱导相关，典型的细胞核浓缩和碎片化、DNA片段化以及质膜外小叶上磷脂酰丝氨酸的暴露证明了这一点。所有这些结果表明，川楝素可能是一种潜在的抗癌药物候选物。
