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Hepato-gastroenterology 2007-Sep

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.

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Toshie Okada
Tokihiko Sawada
Tatsushi Osawa
Masakazu Adachi
Keiichi Kubota

Keywords

Abstract

OBJECTIVE

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.

METHODS

Two HCC lines, HuH7 and Hep3B, were cultured with MK615 at concentrations of 600, 300, 150, and 0 microg/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 microg/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.

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