Conjugated Linoleic Acid Inhibits Proliferation and Modulates Protein Kinase C Isoforms in Human Prostate Cancer Cells

Abstract

Abstract: Prostate cancer is the second most common cancer in men. The disease etiology is poorly understood, but diet and lifestyle are contributory factors. Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products, have antitumor properties in animal models of cancer and antiproliferative effects on cancer cells in vitro. The cellular mechanisms by which CLAs elicit these effects are unclear, particularly for prostate cancer cells. We have previously identified protein kinase C (PKC) isoforms α, δ, ι, μ, and ζ in LNCaP prostate cancer cells. The objective of this study was to determine the effects of CLAs (individual cis-9, trans-11 and trans-10, cis-12 isoforms and a 50:50 mixture) on PKC isoform abundance in LNCaP cells. Confluent cells were treated with 6, 25, and 50 μM CLA for 0.5, 6, and 24 h. Cytosol and membrane protein fractions were assayed for PKC isoforms (mainly α and δ but also ι, μ, and ζ) by Western blot analysis using specific antibodies. CLAs clearly modulated the abundance of these PKC isoforms, both positively and negatively, depending on the isoform, concentration of CLAs, and period of treatment. Increased PKC-δ and decreased PKC-ι membrane abundance was consistent with CLAs eliciting increased apoptosis and, in part, with their antitumor effects.