Luteolin Inhibits Prostate Cancer Cells through Epigenetic Control of Key Genes

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A recent study published in the Journal of Steroid Biochemistry and Molecular Biology has identified the regulation of cell cycle and RNA transcription genes in PC-3 human prostate cancer cells treated with luteolin. The research reveals that luteolin significantly inhibits prostate cancer cells in vitro and in vivo, but the molecular mechanism behind this effect was poorly understood. To elucidate this, cRNA microarray analyses were performed on 38,500 genes to determine the genes altered by luteolin treatment.

Key Takeaways:

  • The expression of 3331 genes was changed greater than 1.2-fold after luteolin treatment, indicating a significant impact on gene expression.
  • Two pathways significantly affected by luteolin were identified: the Cell Cycle Pathway and the RNA Transcription Pathway.
  • In the Cell Cycle Pathway, 22 genes were down-regulated, including polo-like kinase 1, cyclin A2, and proliferation cell nuclear antigen, while one gene, cyclin-dependent kinase inhibitor 1B, was up-regulated.
  • In the RNA Transcription Pathway, 13 genes were down-regulated by luteolin.
  • Real-time polymerase chain reactions and western blots verified the observations from the microarray, confirming the effects of luteolin on gene expression.
  • Two synthetic, chemically distinct type II ligands, ZN-2 and BMHPC, mimicked the effects of luteolin on gene expression at the mRNA and protein level in PC-3 cells.
  • Chromatin immunoprecipitation assays indicated that luteolin exerts its effects on genes by altering the acetylation state of promoter-associated histones.

Statistics:

  • 3331 genes were changed greater than 1.2-fold after luteolin treatment, representing a significant alteration of gene expression.
  • The Cell Cycle Pathway and the RNA Transcription Pathway were significantly affected by luteolin, with 22 and 13 genes down-regulated, respectively.
  • Real-time polymerase chain reactions and western blots confirmed the effects of luteolin on gene expression, with a high degree of accuracy.

Sources:

  • K. Shoulars et al. (2010). Regulation of cell cycle and RNA transcription genes identified by microarray analysis of PC-3 human prostate cancer cells treated with luteolin. Journal of Steroid Biochemistry and Molecular Biology, 118(1-2), 41-50.
  • Prostate Cancer Therapy.
  • Baylor College of Medicine, Dept. of Molecular and Cellular Biology, Houston, TX 77030 USA.
  • Health & Medicine Week editors. (2010). Luteolin Inhibits Prostate Cancer Cells through Epigenetic Control of Key Genes. NewsRx.com.