Richard J Head, Director, CSIRO P-Health National Flagship

Prof. Richard Head is a pharmacologist and currently Director of CSIRO's P-Health National Flagship and Affiliate Professor in the Department of Clinical and Experimental Pharmacology at the University of Adelaide.  Formerly he was Chief of CSIRO's Division of Health Sciences and Nutrition and prior to that Chief of CSIRO's Division of Human Nutrition.  He served as Professor of Pharmacology and Toxicology at West Virginia University Medical Centre, a Research Fellow with the Department of Medicine at the University of Melbourne and Postdoctoral Fellow at the Roche Institute of Molecular Biology.  Professor Head is a Member of numerous professional organisations and has extensive experience in research and research management.  His current research includes approaches to understanding the protective action of dietary constituents in human health.
Prof. Richard Head has authored and co-authored over 100 peer-reviewed papers.

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Abstract

STARCH FERMENTATION, GUT BACTERIA AND GENOMICS

RJ Head1, LJ Cosgrove2, T Lewanowitsch2, MH Zucker2, CA Kerr3 and BM Hines3, CSIRO Preventative Health Flagship1, CSIRO Division of Molecular and Health Technologies2 and CSIRO Livestock Industries3, PO Box 10041, Adelaide BC SA 5000, Australia

One of the principal products of resistant starch fermentation in the colon, butyrate (Bu), induces apoptosis in colorectal cancer cell lines.  We have demonstrated that Bu induces apoptosis in HT29 (colorectal adenoma) and HCT116 (colorectal adenocarcinoma).  HT29 cells were more resistant to apoptosis but not suppression of cell proliferation induced by 5mM Bu.  Using flow cytometry the "apoptotic" response after 48 hours was 2.63% apoptosis, 4.9% necrosis for HT29 cells compared with 4.97% apoptosis and 23-39% necrosis for HCT116 cells.
Inhibition of G-protein function with GP2A (Gq) and PTX (Gi/o) blocked the effects of Bu in HT29 cells but not in HCT116 cells.  RTPCR revealed expression of Bu receptor (GPCR43) in HT29 but not in HCT116 cells.  The Bu carrier MCT-1 was expressed in both cells.  Glut-1 expression was identified in the HCT116 cells.
Collectively the results highlight the role of the colonic fermentation product Bu in inducing apoptosis in colorectal cancer cells in vitro with cells reflecting different stages of the disease.  They also highlight the potential interplay of GPCRs and the glucose transporter Glut-1 in tumor progression.
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