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

Hepatogastroenterology. 2007 Sep;54(78):1770-4.

Abstract

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 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.

MeSH terms

  • Aurora Kinases
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Liver Neoplasms / drug therapy*
  • Plant Extracts / pharmacology*
  • Protein Serine-Threonine Kinases / metabolism*
  • Prunus / metabolism*
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology

Substances

  • MK615 extract
  • Plant Extracts
  • Tetrazolium Salts
  • Thiazoles
  • L-Lactate Dehydrogenase
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • thiazolyl blue