Superior anticarcinogenic activity of trans,trans-conjugated linoleic acid in N-methyl-N-nitrosourea-induced rat mammary tumorigenesis.
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 gamma 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.
Islam
Mohammad A
MA
Division of Applied Life Science (BK21 Program), Graduate School, Gyeongsang National University, Jinju, Republic of Korea.
Kim
Young S
YS
Oh
Tae W
TW
Kim
Gon S
GS
Won
Chung K
CK
Kim
Hoon G
HG
Choi
Myung S
MS
Kim
Jeong O
JO
Ha
Yeong L
YL
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D008770:Methylnitrosourea / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D044243:Linoleic Acids, Conjugated; D008770:Methylnitrosourea