Five-(Tetradecyloxy)-2-furoic Acid Alleviates Cholangiocarcinoma Growth by Inhibition of Cell-cycle Progression and Induction of Apoptosis.

Abstract

Cholangiocarcinoma (CCA), a biliary cancer, is a health problem worldwide. The major problem in CCA treatment presents limited options. To date, targeting cancer metabolism is a promising anti-cancer strategy. To elucidate the functional importance of lipid metabolism in CCA, de novo lipogenesis was inhibited using 5-(tetradecyloxy)-2-furoic acid (TOFA), an acetyl CoA carboxylase inhibitor. Anti-proliferative effects of TOFA were determined both in vitro and in vivo. Its inhibitory effect on cell-cycle and apoptosis was investigated by flow cytometry and western blot analysis of relevant markers. TOFA inhibited CCA cell growth, induced cell-cycle progression accompanied by apoptosis in a dose-dependent manner. Induction of p21, and caspase-3, -8, and -9 cleavages, while down-regulation of cyclin B1 and cyclin D1 were observed in TOFA-treated cells. The therapeutic potential was demonstrated in vivo. De novo lipogensis is essential for CCA cell growth and is an alternative target for CCA treatment.