Diallyl disulfide inhibits N-acetyltransferase activity and gene expression in human esophagus epidermoid carcinoma CE 81T/VGH cells.
Individuals can be classified into rapid or slow acetylators based on the N-acetyltransferase (NAT) activity which is believed to affect cancer risk that is related to environmental carcinogen exposure. Diallyl disulfide (DADS) is a naturally occurring organosulfur compound, from garlic (Allium sativum), which exerts anti-neoplasm activity. In this study, we investigated the inhibitory effects of DADS on NAT activity and gene expresseion (NAT mRNA) in human esophagus epidermoid carcinoma CE 81T/VGH cells. NAT activity was measured by the amounts of N-acetylation of 2-aminofluorene (AF) and non-acetylation of AF by high performance liquid chromatography on cells treated with or without DADS. The amounts of NAT enzymes were examined and analyzed by Western blot. NAT gene expression (NAT mRNA) was examined by polymerase chain reaction and cDNA microarray. DADS decreased the amount of N-acetylation of AF in human esophagus epidermoid carcinoma CE 81T/VGH cells in a dose-dependent manner. Western blot analysis indicated that DADS decreased the levels of NAT protein in CE 81T/VGH cells. PCR and cDNA microarray experiments showed that DADS affected NAT1 mRNA expression in CE 81T/VGH cells. DADS affect NAT activity due to the inhibition of gene expression (NAT1 mRNA) and the decreasing of the protein levels of NAT in CE 81T/VGH cells.
Yu
Fu-Shun
FS
School of Dentistry, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan, ROC.
Yu
Chun-Shu
CS
Lin
Jing-Pin
JP
Chen
Ssu-Ching
SC
Lai
Wan-Wen
WW
Chung
Jing-Gung
JG
D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C028009:diallyl disulfide; D000123:Acetyltransferases