Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells

Abstract

Conjugated linolenic acids (CLN) are geometric and positional isomers of linolenic acid. Growth inhibition and apoptosis induction by alpha-eleostearic acid (c9,t11,t13-CLN), beta-eleostearic acid (t9,t11,t13-CLN), alpha-calendic acid (t8,t10,c12-CLN) and beta-calendic acid (t8,t10,t12-CLN) were compared. beta-Eleostearic acid and beta-calendic acid, which have all-trans-conjugated double bonds, exerted stronger growth inhibition and more DNA fragmentation, an indicator of apoptosis induction, in the human colon cancer cells Caco-2 than alpha-eleostearic acid and alpha-calendic acid with the cis configuration. Down-regulation of bcl-2 and up-regulation of bax mRNA by beta-eleostearic acid were also greater than by alpha-eleostearic acid. Interestingly, the cytotoxic effects of beta-eleostearic acid and beta-calendic acid were not counteracted completely by alpha-tocopherol, whereas the cytotoxic effects of alpha-eleostearic and alpha-calendic acids were lost in the presence of alpha-tocopherol. These results suggest that beta-eleostearic and beta-calendic acids have signaling pathways different from those of alpha-eleostearic and alpha-calendic acids and exhibit high potency for reducing the cell viability of Caco-2.