Metabolic reprograming in cancers is one of cancer hallmarks that allow cancer cell to expand and metastasize to other organs. In collaboration with Assoc Prof Kulthida Vaeteewoottacharn’s research team at Department of Medicine, Khon-Kaen University, they found that the acetyl-CoA carboxylase (ACC) is an essential enzyme that support growth of cholangiocarcinoma (CCA). By using ACC inhibitor namely, Five-(Tetradecyloxy)-2-furoic Acid (TOFA) to treat several CCA cell lines, this chemical inhibitor was found to inhibit 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. Therefore, to demonstrate the therapeutic potential of TOFA, its effect was investigated in CCA-transplanted immunodeficient mice. The KKU-213A cell line was selected as the representative model due to its moderate resistance. TOFA was given intraperitoneally at 20 mg/kg daily for 17 days. The results showed that TOFA potentially suppressed CCA growth in vivo. This finding indicates that the de novo lipogenesis is essential for CCA cell growth and is an alternative target for CCA treatment.
Boonnate P, Kariya R, Saranaruk P, Cha’on U, Sawanyawisuth K, Jitrapakdee S, Okada S, Vaeteewoottacharn K. Five-(Tetradecyloxy)-2-furoic Acid Alleviates Cholangiocarcinoma Growth by Inhibition of Cell-cycle Progression and Induction of Apoptosis. Anticancer Res. 2021 Jul;41(7):3389-3400. doi: 10.21873/anticanres.15126.DOI: 10.21873/anticanres.15126
|Prof. Sarawut Jitrapakdee