Thongphasuk Piyanut, Stremmel Wolfgang, Chamulitrat Walee
Department of Gastroenterology and Infectious Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 345 EG, Heidelberg, Germany.
Chemotherapy. 2009;55(1):42-8. doi: 10.1159/000175466. Epub 2008 Nov 21.
We have shown that compared with silybin, 2,3-dehydrosilybin (DHS) exhibits more potent in vitro anticancer activities alone or in combination with tumor necrosis factor (TNF)-alpha. Since TNF-alpha sensitization is related to DNA topoisomerase (topo) inhibition, DHS may be a potent topo inhibitor.
Under significant apoptosis induction by DHS, we measured specific topo I activity in nuclear extracts or purified enzyme.
Treatment of more transformed FIB cells with 30 microM DHS for 24 h caused significant decreases in topo I activity in nuclear extracts while silybin did not have any effects. Less transformed EPI cells were more resistant against DHS-induced topo I inhibition. Inhibitory effects of topo I activity by DHS were also found in cell-free assays using purified topo I, whereas silybin again did not have any effects.
DHS is a potent topo I inhibitor rendering its ability to sensitize TNF-alpha for enhanced cytotoxicity.
我们已经表明，与水飞蓟宾相比，2,3-脱氢水飞蓟宾（DHS）单独或与肿瘤坏死因子（TNF）-α联合使用时表现出更强的体外抗癌活性。由于TNF-α致敏与DNA拓扑异构酶（拓扑异构酶）抑制有关，DHS可能是一种有效的拓扑异构酶抑制剂。
在DHS显著诱导细胞凋亡的情况下，我们测量了核提取物或纯化酶中的特异性拓扑异构酶I活性。
用30 microM DHS处理转化程度更高的FIB细胞24小时，导致核提取物中拓扑异构酶I活性显著降低，而水飞蓟宾没有任何影响。转化程度较低的EPI细胞对DHS诱导的拓扑异构酶I抑制更具抗性。在使用纯化拓扑异构酶I的无细胞试验中也发现了DHS对拓扑异构酶I活性的抑制作用，而水飞蓟宾同样没有任何影响。
DHS是一种有效的拓扑异构酶I抑制剂，使其能够使TNF-α致敏以增强细胞毒性。
