Superior Anticarcinogenic Activity of trans,trans-Conjugated Linoleic Acid in N-Methyl-N-nitrosourea-Induced Rat Mammary Tumorigenesis

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• 作者：Mohammad A. Islam ; Young S. Kim ; Tae W. Oh ; Gon S. Kim ; Chung K. Won ; Hoon G. Kim ; Myung S. Choi ; Jeong O. Kim ; Yeong L. Ha
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2010
• 出版时间：May 12, 2010
• 年：2010
• 卷：58
• 期：9
• 页码：5670-5678
• 全文大小：987K
• 年卷期：v.58,no.9(May 12, 2010)
• ISSN：1520-5118

文摘

The anticarcinogenic activity of a mixture of trans,trans-conjugated linoleic acid (trans,trans-CLA) was investigated in rat mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU), with references to cis-9,trans-11-CLA and trans-10,cis-12-CLA isomers. Female, 7-week-old Sprague−Dawley rats were intraperitoneally injected with MNU (50 mg/kg of body weight) and then subjected to one of five diets (control, 1% trans,trans-CLA, 1% cis-9,trans-11-CLA, 1% trans-10,cis-12-CLA, and 1% linoleic acid; 8 rats/group) for 16 weeks. Food and water were made available ad libitum. trans,trans-CLA significantly (p < 0.05) reduced tumor incidence, number, multiplicity, and size and significantly (p < 0.05) increased apoptosis, relative to cis-9,trans-11-CLA and trans-10,cis-12-CLA. The molecular mechanism of trans,trans-CLA was elucidated by measuring apoptosis-related gene products and fatty acid composition in tumors. trans,trans-CLA led to increases in the p53 protein and Bax protein levels but suppressed the expression of Bcl-2 protein. The activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase, which resulted in the execution of apoptosis. In addition, trans,trans-CLA reduced cytosolic phospholipase A2, cyclooxygenease-2, and peroxisome proliferator-activated receptor γ protein levels. These results suggest that the trans,trans-CLA inhibits MNU-induced rat mammary tumorigenesis through the induction of apoptosis in conjunction with the reduction of arachidonic acid metabolites and that the efficacy of trans,trans-CLA is superior to cis-9,trans-11-CLA and trans-10,cis-12-CLA.