Thongphasuk Piyanut, Stremmel Wolfgang, Chamulitrat Walee
Faculty of Pharmaceutical Chemistry, Rangsit University, Bangkok, Thailand.
Chemotherapy. 2008;54(1):23-30. doi: 10.1159/000112314. Epub 2007 Dec 7.
Silybin (SIL) exhibits anticancer properties and has now entered clinical trials. In this study, anticancer effects of 2,3-dehydrosilybin (DHS) were compared with SIL either alone or in combination with TNF-alpha.
Cell cytotoxicity identified as apoptosis and necrosis was measured based on DNA fragment sizes using flow cytometry and DNA laddering.
After 24 h treatment,DHS at 30-50 microM markedly induced mainly apoptosis in transformed HepG2 and FIB cells. DHS induced necrosis markedly in HT29 but marginally in less transformed EPI cells. We found that apoptosis was the major mode of cell death when DHS was used in combination with TNF-alpha after 6 h treatment. TNF-alpha could promote DHS-induced apoptosis in HepG2, HT29 and FIB cells, but not in EPI cells. SIL could not reproduce this TNF-alpha-enhanced apoptosis.
Our data provide evidence for the therapeutic use of DHS as an anticancer agent which is more effective than SIL.
水飞蓟宾（SIL）具有抗癌特性，目前已进入临床试验阶段。在本研究中，对2,3 - 脱氢水飞蓟宾（DHS）单独使用或与肿瘤坏死因子 - α（TNF - α）联合使用时的抗癌效果与水飞蓟宾进行了比较。
基于DNA片段大小，使用流式细胞术和DNA梯状条带分析来测定被鉴定为凋亡和坏死的细胞毒性。
处理24小时后，30 - 50微摩尔的DHS主要在转化的HepG2和FIB细胞中显著诱导凋亡。DHS在HT29细胞中显著诱导坏死，但在转化程度较低的EPI细胞中仅轻微诱导坏死。我们发现，处理6小时后，当DHS与TNF - α联合使用时，凋亡是细胞死亡的主要方式。TNF - α可促进DHS诱导的HepG2、HT29和FIB细胞凋亡，但对EPI细胞无此作用。水飞蓟宾不能重现这种TNF - α增强的凋亡现象。
我们的数据为DHS作为一种比水飞蓟宾更有效的抗癌药物的治疗应用提供了证据。
