Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity.
The cytotoxic activity of Brostallicin was previously shown to be enhanced in the presence of high glutathione and glutathione transferase levels. We hypothesized that thiol antioxidants, N-acetylcysteine and Silibinin, could potentiate Brostallicin's cytotoxicity in a similar way. HepG2 and CNE-2 cells were treated with N-acetylcysteine, Silibinin and Brostallicin, either alone or in combination. Surprisingly, we found that NAC and Silibinin had adverse effects on Brostallicin's cytotoxicity. The mechanism underlying the interaction involved the apoptotic pathway as we demonstrated an increase in Bcl-2 protein levels and decrease in caspase 3 activity with the Silibinin-Brostallicin combination.
Pook
Sim-Hwee
SH
Department of Surgery, National University of Singapore, Singapore.
Toh
Chee-Keong
CK
Mahendran
Ratha
R
D000111:Acetylcysteine / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004336:Drug Antagonism; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D006146:Guanidines; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D012838:Silymarin; D013438:Sulfhydryl Compounds; D000077385:Silybin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C455279:brostallicin; D000111:Acetylcysteine