Background: 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.
Methods: Under significant apoptosis induction by DHS, we measured specific topo I activity in nuclear extracts or purified enzyme.
Results: 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.
Conclusion: DHS is a potent topo I inhibitor rendering its ability to sensitize TNF-alpha for enhanced cytotoxicity.
(c) 2008 S. Karger AG, Basel.