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.
Song
Hyun-Ju
HJ
The Robert Gordon University, School of Life Sciences, St. Andrews Street, Aberdeen, United Kingdom.
Sneddon
Alan A
AA
Heys
Steven D
SD
Wahle
Klaus W J
KW
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