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Wei-Jen Chen (Associate Professor, Ph. D.)
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Wei-Jen Chen

(Associate Professor; Ph. D)


Phone

Tel(Office):886-4-2473-0022 ext 11808

E-mail

cwj519@csmu.edu.tw

Interests in Research

Epithelial-mesenchymal transition (EMT), a reversibly cellular process where an epithelial cell loses cell-cell contacts and acquires mesenchymal features, has recently been implicated in the onset of invasive behavior during tumor progression and metastasis. Oncogenic EMT can be induced by EMT regulators including Snail, Slug and Twist along with some signaling pathways, such as Wnt/β-catenin, with poor clinical outcomes. Therefore, inhibition or reversion of EMT mediated by Wnt/β-catenin signaling might be an accessible strategy to reduce the incidence of malignant tumors. Resveratrol, a naturally occurring stilbene phytoalexin from berries and grapes, has been suggested as a potential cancer preventive agent due to its diverse antitumor activity including anti-oxidation, anti-inflammation, anti-proliferation, anti-angiogenesis and induction of apoptosis. However, the effects of resveratrol on EMT in epithelia-derived tumor remain unclear yet. Our previous studies suggest that introduction of methoxy groups on the phenyl ring motif of resveratrol might increase its pro-apoptotic and growth-inhibitory activities. Thus, our research project will determine and compare the capacity of resveratrol and its methoxylated derivatives on Wnt/β-catenin-modulated EMT, and explore the action mechanisms responsible for these effects.

Experimental designs will be divided into three parts to perform: (i) First, we will investigate the effect of resveratrol and its methoxylated derivatives on the regulation of Wnt/β-catenin signaling, EMT and invasion of human MCF-7 or MDA-MB-231 breast adenocarcinoma cell lines. (ii) To evaluate the anti-EMT capacity of resveratrol and its methoxylated derivatives in vivo, an animal model of azoxymethane-induced aberrant crypt foci (ACF) and colon carcinogenesis will be applied to define whether resveratrol and its methoxylated derivatives suppress azoxymethane-induced Wnt/β-catenin activation and prevent normal colonic tissues undergoing EMT and malignant progression, i.e. ACF and colorectal adenoma. (iii) To elucidate whether resveratrol and its methoxylated analogues suppress xenograft tumor metastasis in vivo, human breast cancer cells will be xenotransplanted into inguinal mammary fat pad in nude mice, with intraperitoneal injection of test compounds. Then we will determine the effects and the possible mechanisms involving modulation of Wnt/β-catenin pathway and EMT of resveratrol and its methoxylated derivatives on xenograft tumor growth and lung metastasis. With the research efforts, we hope to define new cancer chemopreventive mechanisms of dietary polyphenolics and provide novel information for synthetic chemists to design new anti-cancer agents against mesenchyme-like malignant tumors.

Publications (at most 7 publications in recent 5 years)

  • Liu, C. B., Chen, L. H., Cheng, A. C., Chen, W. J., Tsai, M. L., Liu, Y., Ho, C. T. and Pan, M. H. (2011). Hexahydro-β-acids induce apoptosis through mitochondrial pathway, GADD153 expression, and caspase activation in human leukemia cells. Food and Chemical Toxicology. Vol. 49, pp. 1033-1042.

  • Pan, M. H., Hong, H. M., Lin, C. L., Jhang, A. Z., Tsai, J. H., Badmaev, V., Nagabhushanam, K., Ho, C. T. and Chen, W. J. (2011). Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages. Molecular Nutrition and Food Research. Vol. 55, pp. 723-732.

  • Pan, M. H., Lin, C. L., Tsai, J. H., Ho, C. T. and Chen, W. J. (2010). 3,5,3’,4’,5’-Pentamethoxystilbene (MR-5), a Synthetically Methoxylated Analogue of Resveratrol, Inhibits Growth and Induces G1 Cell Cycle Arrest of Human Breast Carcinoma MCF-7 Cells. Journal of Agricultural and Food Chemistry. Vol. 58, pp. 226-234.

  • Pan, M. H., Lin, Y. T., Lin, C. L., Wei, C. S., Ho, C. T. and Chen, W. J. (2009). Suppression of Heregulin-β1/HER2-Modulated Invasive and Aggressive Phenotype of Breast Carcinoma by Pterostilbene via Inhibition of Matrix Metalloproteinase-9, p38 Kinase Cascade and Akt Activation. Evidence-based Complementary and Alternative Medicine. Epub ahead of print: eCAM Advance Access published on Jul 16, 2009; doi:10.1093/ecam/nep093.

  • Pan, M. H., Chiou, Y. S., Chen, W. J., Wang, J. M., Badmaev, V. and Ho, C. T. (2009). Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis. Vol. 30, pp. 1234-1242.

  • Chen, W. J., Huang, Y. T., Wu, M. L., Huang, T. C., Ho, C. T. and Pan, M. H.* (2008). Induction of apoptosis by vitamin D2, ergocalciferol, via reactive oxygen species generation, glutathione depletion, and caspase activation in human leukemia Cells. Journal of Agricultural and Food Chemistry. Vol. 56, pp. 2996-3005.

  • Pan, M. H., Lin, C. C., Lin, J. K. and Chen, W. J. (2007). Tea polyphenol EGCG suppresses heregulin-β1-induced fatty acid synthase expression in human breast cancer cells by inhibiting PI3K/Akt and MAPK cascade signaling. Journal of Agricultural and Food Chemistry. Vol. 55, pp. 5030-5037.