Effect of trans, trans conjugated linoleic acid (CLA) isomers on benzo(a)pyrene-induced mouse forestomach neoplasia
trans, trans CLA 이성체 마우스 위종양;
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Conjugated linoleic acid (CLA) is a collective term of octadecadienoic acid (C18:2) with positional (7,9; 8,10; 9,11;10,12; 11,13; and 12,14) and stereoisomeric (t,c; c,t; c,c; and t,t) isomers. CLA synthesized from linoleic acid (LA) by alkaline isomerization contains t10,c12 CLA and c9,t11 CLA isomers as major isomers and t10,t12 CLA and t9,t11 CLA isomers as minor constituents. The synthetic CLA, containing all possible isomers, exhibits many positive biological activities, including anticancer; however, the biological activities of individual CLA isomers are not clearly understood, except that t10,c12 CLA exhibited more stronger body fats reduction in animals and human than c9,t11 CLA. In the present study, anticarcinogenic activity of a mixture of t,t CLA isomers (designated t,t CLA) was studied in female ICR mouse forestomach carcinogenesis model induced by benzo(a)pyrene (BP) with references to c9,t11 CLA, t10,c12 CLA, and synthetic CLA. The t,t CLA (99%) with composition of 14.0% BF3/methanol, consisted of 2.6% t12,t14, 10.7% t11,t13, 36.7% t10,t12, 38.2% t9,t11, 9.5% t8,t10, and 2.3% t7,t9 CLA did not show any chronic and acute toxicity in ICR female and male mice. The t,t CLA strongly inhibited the initiation of BP-induced female ICR mouse forestomach neoplasia relative to c9,t11 CLA, t10,c12 CLA, and synthetic CLA by the mechanistic action of apoptotic induction. Total number of tumors, number of tumors per mouse, and average tumor size in t,t CLA-treated mice was significantly reduced, relative to that of mice treated with synthetic CLA, c9,t11 CLA, or t10,c12 CLA. Tumor incidence was not affected as compared to other CLA isomers. These results might be derived from the complicated facts that t,t CLA enhanced the fragmentation of DNA, apoptotic index (35.46±4.5%), Bax gene and caspase-3 enzyme activity in conjunction with the suppression of Bcl-2 gene expression. These series of experimental studies suggest that t,t CLA without any adverse effects of chronic and acute toxicity in mouse could be useful materials for the reduction of BP-induced mouse forestomach neoplasia.