s-allylcysteine and Carcinoma--Squamous-Cell

We investigated the chemopreventive effect of S-allylcysteine (SAC), a water-soluble garlic constituent against gastric carcinogenesis induced in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl). The animals were divided into four groups of six animals. Rats in groups 1 and 2 were administered MNNG (200 mg/kg body weight) on days 0 and 14 as well as S-NaCl (1 mL/rat) three days during weeks 0 to 3, and thereafter placed on basal diet until the end of the experiment. Rats in group 2 in addition received SAC (200 mg/kg body weight) three times per week starting on the day following the first exposure to MNNG and continued until the end of the experimental period. Group 3 animals were given SAC alone as in group 2. Group 4 animals received basal diet and tap water throughout the experiment and served as the untreated control. The animals were sacrificed after an experimental period of 21 weeks. Measurement of lipid peroxidation and antioxidants of the glutathione redox cycle in the stomach tissue, liver and venous blood was used to monitor the chemopreventive potential of SAC. All animals that received MNNG and S-NaCl alone, developed tumours, identified histologically as squamous cell carcinomas. In the tumour tissue, diminished lipid peroxidation was accompanied by increase in reduced glutathione (GSH) and GSH-dependent enzymes, whereas in the liver and circulation, enhanced lipid peroxidation was associated with antioxidant depletion. Administration of SAC suppressed the incidence of MNNG+S-NaCl-induced gastric tumours as revealed by the absence of carcinomas. SAC ameliorated MNNG-induced decreased susceptibility of the gastric mucosa to lipid peroxidation, whilst simultaneously increasing the antioxidant status. In the liver and blood, SAC reduced the extent of lipid peroxidation and significantly enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive effects by modulating lipid peroxidation and enhancing GSH-dependent antioxidants in the target organ as well as in the liver and blood.

Topics: Animals; Antineoplastic Agents; Antioxidants; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cysteine; Disease Models, Animal; Gastric Mucosa; Glutathione; Lipid Peroxidation; Liver; Male; Methylnitronitrosoguanidine; Oxidants; Oxidation-Reduction; Rats; Rats, Wistar; Sodium Chloride; Stomach Neoplasms

The effects of S-allylcysteine (SAC) on hepatic lipid peroxidation and antioxidant status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBP) were investigated in male Syrian hamsters. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx) and glutathione S-transferase (GST) and a reduction in reduced glutathione (GSH) levels. Administration of SAC significantly decreased the formation of lipid peroxides and enhanced the levels of antioxidants and detoxifying enzymes. We suggest that the elevation of hepatic GSH and GSH-dependent enzymes by SAC may play a key role in preventing cancer development in the hamster cheek pouch.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antioxidants; Carcinoma, Squamous Cell; Cheek; Cricetinae; Cysteine; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Neoplasms, Experimental; Male; Mesocricetus; Mouth Neoplasms; Protective Agents; Thiobarbituric Acid Reactive Substances

Consumption of garlic has been reported to be associated with decreased risk of cancer. We used the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinoma model to assess the oral chemopreventive potential of S-allylcysteine (SAC), a water-soluble constituent of garlic. Hamsters were divided into four groups of six animals each. The right buccal pouches of the animals in group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in group II were painted with DMBA as in group I and in addition received 200 mg/kg body weight SAC intragastrically three times a week on days alternate to DMBA application. Group III animals received SAC as in group II. Animals in group IV received neither DMBA nor SAC and served as control. The hamsters were killed after an experimental period of 14 weeks. Biochemical measurements were carried out on tumour and normal pouch tissues. Measurement of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone for 14 weeks developed well-differentiated squamous cell carcinomas. Diminished lipid peroxidation in the oral tumour tissue was accompanied by a significant increase in the levels of GSH, GPx and GST. Administration of SAC significantly suppressed DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms. The results of the present study suggest that garlic may exert its chemopreventive effects by modulating lipid peroxidation and enhancing the levels of GSH, GPx and GST.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Analysis of Variance; Animals; Antineoplastic Agents; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Cysteine; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Male; Mouth Neoplasms

Factors controlling glutathione metabolism may govern sensitivity to chemotherapeutic agents such as cisplatin. Using a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas, we examined cisplatin resistance relative to (a) glutathione-S-transferase (GST)-pi gene amplification and expression, (b) basal and inducible GST-total and GST-pi enzymatic activity, and (c) cellular levels of reduced glutathione (GSH). Using Southern blot analysis and northern blot hybridization, no relationship between GST-pi gene amplification, mRNA expression and drug resistance could be identified. Despite the capacity of cisplatin to induce GST enzyme activity, the response was variable and unrelated to cisplatin responsiveness. However, an inverse relationship between GSH levels and cisplatin sensitivity was identified. To further clarify these effects, cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum), which altered cellular GSH in a biphasic manner. Pretreatment with SAC to lower cellular GSH levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth.

Topics: Carcinoma, Squamous Cell; Cell Survival; Chromosomes, Human, Pair 11; Cisplatin; Cysteine; Gene Amplification; Gene Expression Regulation, Neoplastic; Glutathione; Glutathione Transferase; Head and Neck Neoplasms; Humans; In Vitro Techniques; RNA, Messenger; Tumor Cells, Cultured