Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate.
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 down regulation of integrin beta 6. In addition, feeding phenethyl isothiocyanate induced alternative splicing of gene variants. This study represents the first use of RNAseq to analyze tumors from animals consuming dietary phenethyl isothiocyanate and to identify potential molecular signatures that may explain the cancer protective effect of this compound.
U.S. Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Bovine Functional Genomics Laboratory, Beltsville, MD, USA.
Robert W
RW
Li
CongJun
C
Li
Thomas T Y
TT
Wang
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004032:Diet; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*; D014183:Transplantation, Heterologous
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate