A novel anti-cancer substance, MK615, from ume, a variety of Japanese apricot, inhibits growth of hepatocellular carcinoma cells by suppressing Aurora A kinase activity

Background/Aims: MK615 is an anti-cancer substance extracted from the Japanese apricot. In the present study, the anti-neoplastic effect of MK615 against hepatocellular carcinoma (HCC) was evaluated in vitro, and its mechanism was elucidated. Methodology: Two HCC lines, HuH7 and Hep3B, were cultured with MK615 at concentrations of 600, 300, 150, and 0 mu g/mL. Growth inhibition was evaluated by MTT assay, and killing activity was determined by LDH assay. Cell cycle stages were evaluated by flow cytometry. Expression of Aurora A kinase (Aurora A) was evaluated by real-time PCR and Western blotting, and inhibition of Aurora A activity was determined by HTscan. Results: MK615 inhibited the growth of, and lysed, HuH7 and Hep3B cells in a dose-dependent manner. Cell cycle analysis revealed that MK615 increased the population of cells in G2/M phase. Real-time PCR and Western blotting showed that MK615 suppressed the expression of Aurora A. HTscan assay demonstrated that Aurora A activity was specifically inhibited by 34.3%, 32.9%, and 54.3% at 150, 300, and 600 mu g/mL MK615, respectively. Conclusions: MK615 has an anti-cancer effect against HCC lines in vitro, and the effect is exerted through inhibition of Aurora A activity.