CYTOTOXITY OF THE trans10,cis12 ISOMER OF CONJUGATED LINOLEIC ACID ON RAT HEPATOMA AND ITS MODULATION BY OTHER FATTY ACIDS, TOCOPHEROL, AND TOCOTRIENOL

Abstract

This study was performed to evaluate the isomer-specific cytotoxic effects of conjugated linoleic acid (CLA) on rat hepatoma dRLh-84 cells in vitro. A 10trans,12cis (10t,12c)-CLA showed a strong cytotoxic effect on dRLh-84 cells in culture, whereas no such effect was observed with 9cis,11trans (9c,11t)-CLA or linoleic acid. The optimum concentration for induction of cytotoxicity by 10t,12c-CLA was 5 to 10 microM, but the effect was alleviated at higher concentrations. Coincubation with oleic or palmitoleic acid and 10t,12c-CLA cancelled the cytotoxic effect, but other major saturated or polyunsaturated fatty acids and eraidic acid did not interfere with 10t,12c-CLA-induced cytotoxity. The cytotoxic effect was also alleviated by alpha-tocopherol (alpha-toc) and alpha-tocotrienol but not by any other antioxidant reagent examined. Significant cytotoxicity of 10t,12c-CLA was detected after only a 15-min incubation, and the most noticeable effect was seen after 3 h. After incubation with 10t,12c-CLA at 10 microM, an additional 90 microM of 10t,12c-CLA or 100 microM of alpha-toc was also able to alleviate the cytotoxicity. When cells were treated with 10 microM 10t,12c-CLA for more than 48 h, treatment with additional CLA or alpha-toc could not prevent cell death.

Induction of Apoptotic Cell Death in HL-60 Cells by Jacaranda Seed Oil Derived Fatty Acids

“…We propose the marked reduction of intracellular oleic acid and palmitoleic acid by inhibition of SCD as one of the cytotoxic mechanisms of t10, c12-CLA against cancer cells. Previous studies showed that exogenous oleic acid or palmitoleic acid completely abrogated the action of t10, c12-CLA 11,18 . Interestingly, dietary jacaranda seed oil decreased the delta-9 desaturation index in the liver and adipose tissue and showed inhibitory effects on SCD-1 mRNA expression in the liver of ICR mice 19 .…”

Oleic acid prevents apoptotic cell death induced by trans10, cis12 isomer of conjugated linoleic acid via p38 MAP kinase dependent pathway

“…Therefore, cytotoxicity of t10, c12-conjugated linoleic acid may be explained by the depletion of intracellular oleic acid and palmitoleic acid. In addition to these findings, it has been shown that the cytotoxicity of conjugated linoleic acid can be modulated by linoleic acid (Igarashi and Miyazawa 2001), tocopherol, and tocotrienol (Yamasaki et al 2005b). Therefore, an interaction between conjugated linoleic acid and other food components was an indispensable factor for the regulation of conjugated linoleic acid function.…”

Efficacy of Gamma-glutamylcysteine (GGC) in Ischemia-reperfusion Injury

“…Unexpectedly, cytotoxicity of approximately 40% cell death was observed in cells treated with GGC and 100 lmol/L CLA after 24 h-incubation. Cytotoxicity of CLA, in particular the trans-10, cis-12 CLA isomer, to cancer cells has previously been reported only at low concentrations (5 to 10 lmol/L), but not at high concentrations of the CLA isomer (100 lmol/L total) (Yamasaki et al, 2005). Further investigations are warranted to determine the mechanism of CLA-induced cytotoxicity in interactions between GGC and CLA.…”