Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl

Robert W Li1, CongJun Li, Thomas T Y Wang

  • 1U.S. Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Bovine Functional Genomics Laboratory, Beltsville, MD, USA.

Molecular Carcinogenesis
|February 7, 2012
PubMed

Insights

Phenethyl isothiocyanate, a cancer preventive compound, significantly reduced tumor growth in mice. RNA sequencing revealed key molecular changes in inflammation and extracellular matrix pathways contributing to this protective effect.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Dietary compounds are investigated for cancer prevention.
  • Phenethyl isothiocyanate (PEITC) is a potential cancer preventive agent.
  • Understanding PEITC's molecular mechanisms in vivo is crucial.

Purpose of the Study:

  • To investigate the effect of dietary phenethyl isothiocyanate on tumor xenograft growth in mice.
  • To elucidate the molecular mechanisms underlying PEITC's tumor growth suppression using RNA sequencing.
  • To identify potential molecular signatures associated with PEITC's cancer-protective effects.

Main Methods:

  • Tumor xenografts were grown in mice fed a control diet or a diet supplemented with phenethyl isothiocyanate.
  • RNA sequencing (RNAseq) was employed to analyze gene expression changes in tumors.
  • Bioinformatic analysis was performed on differentially expressed genes to identify affected pathways.

Main Results:

  • Phenethyl isothiocyanate significantly decreased the rate of tumor xenograft growth.
  • RNAseq analysis revealed modulation of inflammation and extracellular matrix pathways.
  • Key gene expression changes included upregulation of IGFBP3, fibronectin, and thyroxine degradation enzyme, and downregulation of integrin beta 6.
  • Phenethyl isothiocyanate also induced alternative splicing of gene variants.

Conclusions:

  • Dietary phenethyl isothiocyanate demonstrates tumor growth-suppressive effects in a mouse xenograft model.
  • Molecular changes in inflammation, extracellular matrix, and alternative splicing pathways are associated with PEITC's cancer-protective action.
  • This study provides the first RNAseq-based molecular insights into the in vivo effects of dietary phenethyl isothiocyanate.