Prevention of chemical carcinogen DNA binding and inhibition of nuclear RNA polymerase activity by organosulfur compounds as the possible mechanisms for their anticancer initiation and proliferation effects.
This report examines the transcriptional roles and DNA binding properties of the three major organosulfur compounds (OSCs) from garlic, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS). We found DADS and DATS, but not DAS, could be activated by the versatile epoxide-forming oxidant dimethyldioxirane (DMDO) and could strongly inhibit nuclear RNA synthesis in vitro. We also found that when incubated together with [3H]-labeled 17beta-estradiol (E(2)) for activation by DMDO, DADS and DATS, but not DAS, were able to prevent the binding of [3H]E(2) to DNA. This preventive effect of DADS and DATS was confirmed when liver microsomes were used, and further verified by 32P post-labeling analysis. Additionally, we discovered that the DMDO treated DADS and DATS, but not DAS, were able to directly inhibit the enzyme RNA polymerase per se. These novel findings provide new insights into the potential mechanisms of the preventive effects of OSCs on tumor initiation and promotion.
Yu
Fu Li
FL
Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, 1601 Parkview Avenue, 61107, Rockford, IL, USA. fuliyu@uic.edu
Bender
Wanda
W
Fang
Qingming
Q
Ludeke
Anna
A
Welch
Brianna
B
D000498:Allyl Compounds / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004220:Disulfides / Q000378:metabolism / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D005737:Garlic; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D004220:Disulfides; D013440:Sulfides; C042577:diallyl trisulfide; D004958:Estradiol; C028009:diallyl disulfide; C038491:allyl sulfide; D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases; D004121:Dimethyl Sulfoxide