Potent direct or TNF-alpha-promoted anticancer effects of 2,3-dehydrosilybin: comparison study with silybin.
BACKGROUND
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.


METHODS
Cell cytotoxicity identified as apoptosis and necrosis was measured based on DNA fragment sizes using flow cytometry and DNA laddering.


RESULTS
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.


CONCLUSIONS
Our data provide evidence for the therapeutic use of DHS as an anticancer agent which is more effective than SIL.
Faculty of Pharmaceutical Chemistry, Rangsit University, Bangkok, Thailand.
Piyanut
P
Thongphasuk
Wolfgang
W
Stremmel
Walee
W
Chamulitrat
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D009336:Necrosis / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin