Induction of apoptosis and inhibition of NF-kappaB activation in human prostate cancer cells by the cis-9, trans-11 but not the trans-10, cis-12 isomer of conjugated linoleic acid.
BACKGROUND
Conjugated linoleic acids (CLAs) have anti-tumorigenic properties in animal models and anti-proliferative effects on cancer cells in vitro. Previous studies have shown that the NF-kappaB pathway is involved regulating anti-apoptotic gene expression. The present study investigated the effects of CLAs (cis-9, trans-11, and trans-10, cis-12 isomers and a 50:50 mixture) on apoptosis and NF-kappaB activation in LNCaP cells.


METHODS
Apoptosis was assessed by annexin V staining using flow cytometry. TNF-alpha-induced NF-kappaB activity was determined by gel shift and reporter gene assays in addition to monitoring IkappaBalpha phosphorylation.


RESULTS
Only the CLA cis-9, trans-11 isomer significantly increased TNF-alpha-induced apoptosis (by 59%), which correlated with a reduction in NF-kappaB transcriptional activity (by 35%, P < 0.05), NF-kappaB binding activity (by 15%, P < 0.05), and phosphorylation of IkappaBalpha (by 36%, P < 0.01).


CONCLUSIONS
Our results may offer a mechanistic explanation for the reported inhibition of prostate tumor growth by CLAs in animal models of disease.
The Robert Gordon University, School of Life Sciences, St. Andrews Street, Aberdeen, United Kingdom.
Hyun-Ju
HJ
Song
Alan A
AA
Sneddon
Steven D
SD
Heys
Klaus W J
KW
Wahle
D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017304:Annexin A5; D004273:DNA, Neoplasm; D020672:I-kappa B Proteins; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha