Submitted to: Molecular Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2012
Publication Date: 5/5/2012
Citation: Li, R.W., Li, C., Wang, T.T. 2012. Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate. Molecular Carcinogenesis. DOI: 10.1002/mc.21873.
Interpretive Summary: The mechanisms underlying the effects of health promoting phytochemicals from broccoli remain unclear. To address these questions USDA scientist utilized RNAseq technology to examine the effects of a broccoli-derived cancer preventive compound phenethyl isothiocyanate. RNAseq technology examined global gene expression in a prostate tumor model in mice fed with 3 µmol/g of phenethyl isothiocyanate. Phenethyl isothiocyanate-treatment led to decreased rate of tumor growth. Bioinfrormatic analysis of differentially expressed genes in the tumors identified a modulation of cellular pathway network involved in inflammation and extracellular matrix formation. In addition, phenethyl isothiocyanate affected alternative splicing of gene variants as compared to the control. This study represents the first use of RNAseq to analyze tumor from animals consuming dietary phenethyl thiocyanate and to identify potential molecular signatures of phenethyl isothiocyanate-induced effects that may explain the cancer protective properties of this compound. The information serves as an important basis for future investigation of efficacies and mechanisms of action of diet-derived, health promoting phytochemicals. This work will benefit basic, as well as translational research science.
Technical Abstract: Temporal growth of tumor xenografts in mice on a control diet was compared to mice supplemented daily with 3 µmol/g of the cancer preventive compound phenethyl isothiocyanate. Phenethyl isothiocyanate decreased the rate of tumor growth. The effects of phenethyl isothiocyanate on tumor growth were examined by RNAseq to elucidate molecular changes that may contribute to tumor growth suppression. Bio-informatic analysis of differentially expressed genes identified changes in inflammation and extracellular matrix pathways that were modulated by treatment with phenethyl isothiocyanate. Specific gene expression changes in these pathways included up-regulation of insulin-like growth factor binding protein 3, fibronectin, thyroxine degradation enzyme and a down regulation of integrin beta 6. In addition, feeding phenethyl isothiocyanate induced alternative splicing of gene variants. This study represents first use of RNAseq to analyze tumor from animals consuming dietary phenethyl thiocyanate and the identification of potential molecular signatures that may explain the cancer protective effect of this compound.