J Cancer 2018; 9(15):2734-2742. doi:10.7150/jca.26374 This issue
Department of Nephrology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd ,Wuhan, 430060, China
Cancer cells usually have a high requirement for fatty acids in order to meet the rapid proliferation and metabolism. Acetyl-CoA carboxylase-α(ACCA) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and has been a rate-limiting enzyme in the synthesis of long chain fatty acid and cellular energy storage. 5-tetradecyloxy-2-furoic acid (TOFA) is well known as an allosteric inhibitor of ACCA. In this study, we examined the functions of TOFA in human renal cell carcinoma (RCC) cell lines ACHN and 786-O. According to the results, TOFA inhibited ACHN and 786-O cell growth in a concentration and time dependent manner. The IC50 values of ACHN and 786-O cells were 6.06 and 5.36 µg/ml by the treatment of TOFA for 48 h, respectively. Flow cytometry analysis showed that TOFA markedly arrest cell cycle at G2/M phase and lead to cell apoptosis. In addition, Western blot results revealed that TOFA decreased the phosphorylation of proteinkinaseB(Akt), Mammalian target of rapamycin (mTOR) and p70 ribosomal protein S6 kinase (p70S6K). What's more, specific phosphoinositide 3-kinases (PI3K) phosphorylation inhibitor LY294002 potentiated TOFA anti-cancer activity. These results suggested that TOFA induces growth restraint and apoptosis via inhibiting the PI3K/Akt/mTOR pathway and TOFA may be a novel therapeutic strategy for RCC treatment.
Keywords: TOFA, Human renal cell carcinoma cell lines, Cell cycle arrest, Cell apoptosis, PI3K/Akt/mTOR