Congulated linoleic acid decreases cellular proliferation and inhibits nuclear factor-kappaB and activator protein 1 activation in PC3 cancerous prostate epithelial cells

The precise etiologic factors that initiate and enhance the progression of prostate cancer remains unknown, but diet and lifestyle factors have come forth as significant contributing factors. Conjugated linoleic acid (CLA) is a family of fatty acid isomers found in ruminant food products that appear to have chemopreventive properties in animal models of cancer and antiproliferative effects in several types of cancer cells. Dysregulation and constitutive activation of nuclear factor-kappaB (NFkappaB) and activator protein 1 (AP1) is found in malignant prostate cells, and dietary components that target these transcription factors may prove to be effective chemopreventive agents. The purpose of this study was to examine the antiproliferative effects of CLA on PC3 cancerous prostate epithelial cells and test the ability of CLA to modulate transcription factors NFkappaB and AP1. We found that a mixture of CLA isomers potently inhibited cellular proliferation of androgen-independent PC3 prostate carcinoma cells in a dose-dependent manner. Electromobility shift assays also revealed that CLA inhibited constitutive activation of NFkappaB and AP1 transcription factors in PC3 cells. Mobility shift assays demonstrated that CLA also induced activation peroxisome proliferator-activated receptors (PPARs). However, time course studies revealed that PPAR activation occurred after inhibitory effects on NFkappaB and AP1, suggesting that inhibition of NFkappaB and AP1 did not depend on PPAR activation. The ability of CLA to attenuate inflammatory processes and cellular proliferation by the inhibition of these transcription factors could be the key in their ability to limit cancer development.