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Combination chemoprevention by diet-derived agents that induce apoptosis is a promising strategy to control gastric cancer, the second most common malignancy worldwide. The present study was undertaken to investigate the apoptosis-inducing potential of a combination of S-allylcysteine (SAC), an organosulphur constituent of garlic and lycopene, a tomato carotenoid during N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) and saturated sodium chloride (S-NaCl)-induced gastric carcinogenesis in Wistar rats using the apoptosis-associated proteins Bcl-2, Bax, Bim, caspase 8 and caspase 3 as markers. Animals administered MNNG followed by S-NaCl developed squamous cell carcinomas of the stomach associated with increased Bcl-2 expression and decreased expression of Bax, Bim, caspase 8 and caspase 3. Although SAC and lycopene alone significantly suppressed the development of gastric cancer, administration of SAC and lycopene in combination was more effective in inhibiting MNNG-induced stomach tumours and modulating the expression of apoptosis-associated proteins. Our results suggest that induction of apoptosis by SAC and lycopene combination represents one of the possible mechanisms that could account for their synergistic chemopreventive activity against gastric cancer.

We investigated "the "chemopreventive potential of lycopene against gastric carcinogenesis induced in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl). Administration of lycopene inhibited MNNG+S-NaCl-induced gastric carcinogenesis as revealed by the absence of carcinomas. Lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) were used to monitor the chemopreventive potential of lycopene. The extent of lipid peroxidation was significantly lower, whereas GSH, GPx, GST and GR were markedly enhanced in the gastric mucosa of tumour-bearing animals. Our data suggest that lycopene may exert its inhibitory effects by modulating the oxidant and antioxidant status in the gastric mucosa.

Chemoprotection by dietary agents is a promising strategy for cancer prevention. The aim of the present study was to evaluate the combined effect of tomato and garlic against 7,12-dimethylbenz-[a]anthracene (DMBA)-induced genetic damage and oxidative stress in 12-14-week-old male Swiss albino mice. The animals were randomized into experimental and control groups and divided into eight groups of five animals each. Group 1 animals were injected intraperitoneally with 35 mg/kg body weight DMBA suspended in peanut oil as a single dose. Groups 2-4 animals received tomato (500 mg/kg body weight), garlic (125 mg/kg body weight) and a combination of tomato and garlic for 5 days by gavage, respectively, followed by DMBA 1.5 h after the final feeding. The doses of tomato and garlic correspond to the average human daily consumption. Animals in groups 5, 6 and 7 received tomato alone, garlic alone and tomato + garlic combination, respectively, for 5 days. Group 8 animals received the same volume of water and served as control. The incidence of bone marrow micronuclei and the extent of lipid peroxidation and the concentrations of antioxidants glutathione, glutathione peroxidase and glutathione-S-transferase were measured in the liver, 48 h after DMBA exposure. Increased frequency of micronuclei and enhanced lipid peroxidation accompanied by compromised antioxidant defenses were observed in DMBA-treated animals. Although pretreatment with tomato or garlic significantly reduced the frequency of DMBAinduced bone marrow micronuclei, the combination of tomato and garlic exhibited more profound effect in inhibiting DMBA-induced genotoxicity and oxidative stress. We suggest that a broad spectrum of antimutagenic and anticlastogenic effects can be achieved through an effective combination of functional foods such as tomato and garlic.

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Combination chemoprevention by diet-derived agents is a promising strategy for protection against gastric cancer. We therefore evaluated the combined chemopreventive effect of S-allylcysteine (SAC), an organosulfur constituent of garlic, and lycopene, a major carotenoid present in tomatoes, against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl)-induced gastric carcinogenesis in Wistar rats. The animals were divided into eight groups of six animals each. Rats in group 1 were given MNNG by intragastric intubation on days 0 and 14 as well as S-NaCl every 3 days during weeks 0-3. Animals in groups 2-4, administered MNNG and S-NaCl as in group 1, received in addition SAC and lycopene alone and in combination, respectively, three times per week starting on the day following the first exposure to MNNG. Groups 5-7 were given the chemopreventive agents alone, whereas group 8 served as controls. 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, liver, and erythrocytes was used to monitor the chemopreventive potential of SAC and lycopene. In the tumor tissue, diminished lipid peroxidation was accompanied by an increase in reduced glutathione (GSH) and GSH-dependent enzymes, whereas in the liver and erythrocytes, enhanced lipid peroxidation was associated with antioxidant depletion. Although SAC and lycopene alone significantly suppressed the development of gastric cancer, administration of SAC and lycopene in combination was more effective in inhibiting MNNG-induced stomach tumors and modulating the redox status in the tumor and host tissues. The results of the present study validate the hypothesis that diet-derived chemopreventive agents such as SAC and lycopene in combination may interact synergistically with high efficacy and lessened toxicity against gastric cancer.

The modifying effects of aqueous extracts of garlic and neem leaf during the pre-initiation and post-initiation phases of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in male Wistar rats. The extent of lipid peroxidation and the status of phase II biotransformation enzymes such as glutathione peroxidase and glutathione-S-transferase that use reduced glutathione (GSH) as substrate were used to biomonitor the chemopreventive potential of these extracts. Enhanced lipid peroxidation in the liver and blood of tumor-bearing animals was accompanied by significant decreases in the activities of GSH-dependent antioxidants in the pre-initiation as well as in the post-initiation phases. Our results suggest that the modulatory effects of garlic and neem leaf on hepatic and blood oxidant-antioxidant status may play a key role in preventing cancer development at extrahepatic sites.

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