2,3-dehydrosilybin is a better DNA topoisomerase I inhibitor than its parental silybin.
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.


CONCLUSIONS
DHS is a potent topo I inhibitor rendering its ability to sensitize TNF-alpha for enhanced cytotoxicity.
Thongphasuk
Piyanut
P
Department of Gastroenterology and Infectious Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 345 EG, Heidelberg, Germany.
Stremmel
Wolfgang
W
Chamulitrat
Walee
W
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D006801:Humans; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D012838:Silymarin; D059004:Topoisomerase I Inhibitors; D014409:Tumor Necrosis Factor-alpha; C515097:dehydrosilybin; D000077385:Silybin; D004264:DNA Topoisomerases, Type I