Effects of Garlic Components Diallyl Sulfide and Diallyl Disulfide on Arylamine N-Acetyltransferase Activity and 2-Aminofluorene-DNA Adducts in Human Promyelocytic Leukemia Cells

Abstract

Two components of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS), inhibited arylamine N-acetyltransferase (NAT) activity and 2-aminofluorene-DNA adduct in human promyelocytic leukemia cells (HL-60). The NAT activity was measured by high performance liquid chromatography assaying for amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Cellular cytosols and intact cell suspensions were assayed. The inhibition of NAT activity and 2-AF-DNA adduct formation in human leukemia cells by DAS and DADS were dose-dependent and were directly proportional. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmax from human leukemia cells in both assays. This is the first report of garlic components affecting human leukemia cell NAT activity and 2-AF-DNA adduct formation.

Prevailing Knowledge on the Bioavailability and Biological Activities of Sulphur Compounds from Alliums: A Potential Drug Candidate

“…A study has been reported that the garlic components DAS and DADS are the effective inhibitors of bladder and colon cancer progression. The in-vitro study has shown that the compounds can inhibit the arylamine N-acetyltransferase (NAT) activity to produce carcinogens from foreign substances, cell growth, and DNA adduct formation of bladder and colon tumour cells in a dose-dependent manner [ 34 , 64 ]. Another garlic compound called allicin was reported to induce the p53 mediated autophagic cell death in Hep G2 liver cancer cells.…”

Phase Ii Drug Metabolizing Enzymes

“…Caffeic acid, esculetin, quercetin, kaemferol and genistein inhibited NAT1 whereas scopuletin and coumarin inhibited NAT2 88 . Chen et al 89 and Lin et al 90 described the effect of diallyl sulfide (DAS) and diallyl disulfide (DADS), major components of garlic, on NAT activity in human colon tumor cells and human promyelocytic leukemia cells. These studies demonstrated that DAS and DADS markedly inhibited NAT activity in these cells and would thus assist the organism in defense against cancer.…”

The Attenuation of Early Benzo(a)Pyrene-Induced Carcinogenic Insults by Diallyl Disulfide (DADS) in MCF-10A Cells

“…DADS inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary cancer in rats by significantly lowering both the ductal carcinoma incidence and multiplicity of total tumors [17]. DADS has demonstrated anticarcinogenic properties in numerous human cancer cell lines including HepG2 hepatoma [18], HL-60 leukemia [19], non-small cell lung cancer [20], SH-SY5Y neuroblastoma [21], MCF-7 breast cancer [22], as well as Caco-2 and HT-29 colon tumor cells [23, 24]. The role of DADS in preventing carcinogenesis in normal cells has not been fully elucidated so further research is needed to evaluate its capacity for inhibiting early stage cancer initiation in non-neoplastic cells.…”