Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse

Abstract

In the present study, eight organosulfur compounds from garlic and onions were studied for their inhibitory effects on benzo[a]pyrene (BP)-induced neoplasia of forestomach and lung of female A/J mice when administered 96 and 48 h prior to carcinogen challenge. These compounds had one, two or three linearly connected sulfur atoms. They included the four allyl group-containing derivatives: allyl methyl trisulfide (AMT), allyl methyl disulfide (AMD), diallyl trisulfide (DAT), and diallyl sulfide (DAS), and also four corresponding saturated compounds in which propyl groups were substituted for the allyl groups. All four allylic compounds inhibited BP-induced neoplasia of the forestomach. The saturated analogs were almost without inhibitory activity, indicating the importance of the allyl groups. DAT, which contains two allyl groups, was more potent than AMT, which contains only one allyl group, thus providing further evidence for the role of allyl groups in the inhibitory effects observed. DAS and AMD, but not DAT or AMT, inhibited pulmonary adenoma formation. The fact that in the lung the monosulfide and disulfide inhibited, but the trisulfide did not inhibit, indicates that the number of sulfur atoms in the molecule can control the organ sites at which protection against carcinogenesis will occur. All four allylic compounds induced increased glutathione S-transferase (GST) activity in the forestomach, but varied in their capacity to induce GST in lung, liver and small bowel. Their saturated analogs produced little or no induction. In evaluating relationships between diet and cancer, it would be useful to consider the possible role of garlic and onion organosulfur compounds as protective agents. In addition, further studies of this class of chemicals might lead to the identification and development of useful new chemopreventive compounds.

Diallyl trisulfide-induced G2–M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc25C

“…Garlic-derived OSCs including diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) have been shown to offer significant protection against cancer in animal models induced by a variety of chemical carcinogens (Wargovich, 1987;Sparnins et al, 1988;Wargovich et al, 1988;Wattenberg et al, 1989;Sumiyoshi and Wargovich, 1990;Takahashi et al, 1992;Reddy et al, 1993;Schaffer et al, 1996;Suzui et al, 1997). For example, cancer chemoprevention by naturally occurring OSC analogues has been observed against benzo [a]pyrene-induced forestomach and pulmonary carcinogenesis in mice (Sparnins et al, 1988), N-nitrosomethylbenzylamine-induced esophageal cancer in rats (Wargovich et al, 1988), and 1,2-dimethylhydrazine-induced colon cancer in mice (Sumiyoshi and Wargovich, 1990).…”

“…For example, cancer chemoprevention by naturally occurring OSC analogues has been observed against benzo [a]pyrene-induced forestomach and pulmonary carcinogenesis in mice (Sparnins et al, 1988), N-nitrosomethylbenzylamine-induced esophageal cancer in rats (Wargovich et al, 1988), and 1,2-dimethylhydrazine-induced colon cancer in mice (Sumiyoshi and Wargovich, 1990).…”

Inhibitory Effects of S‐Methylcysteine and Cysteine on the Promoting Potential of Sodium Phenobarbital on Rat Liver Carcinogenesis

“…The homogenized supernatant was centrifuged at 100 000g for 30 min. The amount of radioactive CO 2 produced from [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]ornithine was assayed to estimate the ODC activity. Statistical analysis Statistical analysis of data was performed by employing Student's t test.…”

“…1,2) Further, it has numerous chemical constituents which inhibit the progression of different types of cancer in experimental chemical carcinogeneses. [1][2][3][4][5][6][7][8][9][10][11] Many reports have emphasized the preventive potential of oilsoluble orangosulfur compounds (OSCs) present in the allium family, on chemical carcinogenesis. [1][2][3][4][5][8][9][10] Watersoluble OSCs, on the other hand, have not been extensively studied.…”

Allyl sulfur compounds and cellular detoxification system: effects and perspectives in cancer therapy

“…Chemopreventive effects of garlic constituents are associated with increased levels of GSH and with both significant increase of GST activity in rats treated with DADS (Demeule et al 2004) and increased levels of GSTa and GSTp in kidney (Dwivedi et al 1996;Guyonnet et al 1999). It has been also observed that the stimulation of hepatic GST by OSCs may require quite a long lag time to evidence an effect (Sumiyoshi and Wargovich 1990;Sparnins et al 1986Sparnins et al , 1988. Although not all GST isozymes are influenced equally and the GST response to OSCs shows organo-specificity, the up-regulation of the GSTp induced by OSCs may represent a particularly important event in the anticarcinogenic properties associated with garlic (Hu and Singh 1997;Tsai et al 2007).…”