Combination of S-allylcysteine and lycopene induces apoptosis by modulating Bcl-2, Bax, Bim and caspases during experimental gastric carcinogenesis.
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.
Velmurugan
B
B
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Mani
A
A
Nagini
S
S
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D018890:Chemoprevention / Q000379:methods; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000077276:Lycopene; D008297:Male; D008769:Methylnitronitrosoguanidine; D009374:Neoplasms, Experimental; D011336:Probability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008769:Methylnitronitrosoguanidine; D002338:Carotenoids; C065299:S-allylcysteine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003545:Cysteine; D000077276:Lycopene