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 α-eleostearic acid (c9,t11,t13-CLN), β-eleostearic acid (t9,t11,t13-CLN), α-calendic acid (t8,t10,c12-CLN) and β-calendic acid (t8,t10,t12-CLN) were compared. β-Eleostearic acid and β-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 α-eleostearic acid and α-calendic acid with the cis configuration. Down-regulation of bcl-2 and up-regulation of bax mRNA by β-eleostearic acid were also greater than by α-eleostearic acid. Interestingly, the cytotoxic effects of β-eleostearic acid and β-calendic acid were not counteracted completely by α-tocopherol, whereas the cytotoxic effects of α-eleostearic and α-calendic acids were lost in the presence of α-tocopherol. These results suggest that β-eleostearic and β-calendic acids have signaling pathways different from those of α-eleostearic and α-calendic acids and exhibit high potency for reducing the cell viability of Caco-2.