Curcumin-induced mitotic spindle defect and cell cycle arrest in human bladder cancer cells occurs partly through inhibition of aurora A

Mol Pharmacol. 2011 Oct;80(4):638-46. doi: 10.1124/mol.111.072512. Epub 2011 Jul 14.

Abstract

Curcumin, an active compound in turmeric and curry, has been proven to induce tumor apoptosis and inhibit tumor proliferation, invasion, angiogenesis, and metastasis via modulating numerous targets in various types of cancer cells. Aurora A is a mitosis-related serine-threonine kinase and plays important roles in diverse human cancers. However, the effect of curcumin on Aurora A has not been reported. In this study, Aurora A promoter activity and mRNA expression were inhibited in curcumin-treated human bladder cancer T24 cells, suggesting that Aurora A is regulated at the transcription level. We also found that curcumin preferentially inhibited the growth of T24 cells, which show a higher proliferation rate, invasion activity, and expression level of Aurora A compared with that of human immortalized uroepithelial E7cells. Furthermore, inhibition of phosphorylation of Aurora A and its downstream target histone H3 accompanied by the formation of monopolar spindle, induction of G(2)/M phase arrest, and reduction in cell division in response to curcumin were detected in T24 cells. These curcumin-induced phenomena were similar to those using Aurora A small interfering RNA and were attenuated by ectopic expression of Aurora A. Therefore, the antitumor mechanism of curcumin is Aurora A-related, which further supports the application of curcumin in treatments of human cancers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Cell Cycle / drug effects*
  • Cell Cycle / physiology
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Dose-Response Relationship, Drug
  • Humans
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / metabolism
  • Spindle Apparatus / drug effects*
  • Spindle Apparatus / enzymology
  • Spindle Apparatus / pathology
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Protein Kinase Inhibitors
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Curcumin