Environmental & Molecular Toxicology

Roderick H. Dashwood

Professor
Dept: EMT/LPI (503 Weniger Hall)
Ph.D. 1986, University of Portsmouth, UK.
Phone: 541-737-5086
Fax: 541-737-5077
Rod.Dashwood@oregonstate.edu
Linus Pauling Institute

The research program in my laboratory seeks to improve our understanding of the molecular and biochemical events associated with the development of colorectal cancer (CRC). Family history can be an important consideration in some individuals, and the study of such diseases as familial adenomatous polyposis (FAP) has provided insights into the genes that play a role in the development of CRC. These include oncogenes such as Ki-ras and Ctnnb1 (β-catenin) and tumor suppressor genes such as APC, as well as genes associated with DNA repair mechanisms. Diet and lifestyle factors (such as regular exercise) also impact in a major way on CRC.

To gain better insight into these risk factors, we use in vitro and whole animal approaches, including transgenic models of CRC. Results to date suggest that chlorophylls (in green, leafy vegetables) and tea polyphenols might be effective in reducing the risk from CRC. Sulforaphane (from broccoli), allyl compounds (from garlic), and various other dietary phytochemicals are also studied as histone deacetylase (HDAC) inhibitors. HDAC inhibitors are receiving increasing interest due to their potential to act as cancer chemopreventive as well as chemotherapeutic agents. Protection during later stages of CRC might involve epigenetic changes in the 'histone code', such as alterations in specific acetylated lysine residues.

Selected Publications

• Myzak MC, Dashwood RH. (2006) Chemoprotection by sulforaphane: Keep one eye beyond Keap1. Cancer Lett. 233(2):208-18.
• Orner GA, Roebuck BD, Dashwood RH, Bailey GS. (2006) Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats. J Carcinog. 5(1):6 [Epub ahead of print]
• Myzak, M.C., Dashwood, W.M., Orner, G.A., Ho, E. and Dashwood, R.H. (2006) Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apcmin mice. FASEB J. [Epub ahead of print].
• Myzak, M.C., Hardin, K., Wang, R., Dashwood, R.H. and Ho, E. (2005) Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP, and PC-3 prostate epithelial cells. Carcinogenesis, [Epub ahead of print].
• Dashwood RH, Myzak MC, Ho E. (2005) Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis. [Epub ahead of print]
• Dashwood WM, Carter O, Al-Fageeh M, Li Q, Dashwood RH. (2005) Lysosomal trafficking of β-catenin induced by the tea polyphenol epigallocatechin-3-gallate. Mutat Res. [Epub ahead of print].
• Yu TW, Xu M, Dashwood RH. (2004) Antimutagenic activity of spearmint. Environ Mol Mutagen. 44(5):387-93.
• Orner GA, Dashwood WM, Dashwood RH. (2004) Tumor-suppressing effects of antioxidants from tea. J Nutr. 2004 Nov;134(11):3177S-3178S.
• Li Q, Dashwood RH. (2004) Activator protein 2α associates with adenomatous polyposis coli/β-catenin and Inhibits β-catenin/T-cell factor transcriptional activity in colorectal cancer cells. J Biol Chem. 279(44):45669-75. Epub 2004 Aug 24.
• Myzak, M., Karplus, P.A., Chung, F.-L. and Dashwood, R.H. (2004) A novel mechanism of chemoprotection by sulforaphane: Inhibition of histone deacetylase. Cancer Res. 64, 5767-5774.
• Al-Fageeh, M., Li, Q., Dashwood W-M., Myzak, M.C. and Dashwood, R.H. (2004) Phosphorylation and ubiquitination of oncogenic mutants of β-catenin containing substitutions at Asp32. Oncogene. 23, 4839-4846.
• Li, Q., Dashwood, W.-M., Al-Fageeh, M., Zhong, X. and Dashwood, R.H. (2004) Cloning of the rat β-catenin gene (Ctnnb1) promoter and its functional analysis compared with Catnb and CTNNB1 promoters. Genomics. 83, 231-242.
• Blum, C.A., Tanaka, T., Zhong, X., Li, Q., Dashwood, W-M., Pereira, C., Xu, M. and Dashwood, R.H. (2003) Mutational analysis of Ctnnb1 and Apc in tumors from rats given 1-2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline: Mutational 'hotspots' and the relative expression of β-catenin and c-Jun. Mol. Carcinog. 36, 195-203.
• Diaz, D., Li, Q. and Dashwood, R.H. (2003) Caspase-8 and AIF mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Cancer Res. 63, 1254-1261.
• Orner, G.A., Dashwood, W-M., Blum, C.A., Diaz, G.D., Li, Q. and Dashwood, R.H. (2003) Suppression of tumorigenesis in the Apcmin mouse: down-regulation of β-catenin signaling by a combination of tea plus sulindac. Carcinogenesis 24, 263-267.