Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells.
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.
Yasui
Yumiko
Y
Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido 041-8611, Japan.
Hosokawa
Masashi
M
Kohno
Hiroyuki
H
Tanaka
Takuji
T
Miyashita
Kazuo
K
D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D008042:Linolenic Acids / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C494826:BAX protein, human; D005231:Fatty Acids, Unsaturated; D008042:Linolenic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C004934:eleostearic acid; C428441:calendic acid; D024502:alpha-Tocopherol