Abstract

Resveratrol has shown a strong chemopreventive effect against cancer. However, the molecular mechanisms by which resveratrol inhibits carcinogenesis are not clear. We will use COX-2 gene knockout mice and JB6, HaCaT and other cell culture systems to examine the anti-tumor promotion effect of resveratrol at the molecular level. Our hypothesis is that the inhibition of skin carcinogenesis by resveratrol occurs through an inhibition of COX-2 activity and induction of cell apoptosis.
The specific aims to address the hypothesis are as follows:
Specific Aim 1. To investigate whether the anti-skin carcinogenesis activity of resveratrol occurs through the COX-2 pathway by using the COX-2+/+ and COX-2-/ mouse model.
Specific Aim 2. To investigate the role of COX-2 in resveratrol-induced cell death (apoptosis).
Specific Aim 3. To determine the structure/activity relationship of resveratrol and its derivatives on cell transformation, apoptosis and phosphatidylinositol-3 (PI-3) kinases. We have established experimental conditions, including COX-2 knockout mice and cell lines, arid synthesis of resveratrol derivatives, in our preliminary studies. Our long-term goal is to identify the molecular mechanism explaining the anti-tumor effect exhibited by resveratrol. Such knowledge will help in developing better chemopreventive agents with fewer side effects. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA111536-02
Application #
7088984
Study Section
Special Emphasis Panel (ZRG1-CDP (01))
Program Officer
Crowell, James A
Project Start
2005-06-30
Project End
2010-04-30
Budget Start
2006-06-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$291,217
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Organized Research Units
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Jung, Sung Keun; Ha, Su Jeong; Jung, Chang Hwa et al. (2016) Naringenin targets ERK2 and suppresses UVB-induced photoaging. J Cell Mol Med 20:909-19
Jung, Sung Keun; Lee, Mee-Hyun; Lim, Do Young et al. (2015) Butein, a novel dual inhibitor of MET and EGFR, overcomes gefitinib-resistant lung cancer growth. Mol Carcinog 54:322-31
Bode, Ann M; Dong, Zigang (2015) Toxic phytochemicals and their potential risks for human cancer. Cancer Prev Res (Phila) 8:1-8
Oi, N; Yuan, J; Malakhova, M et al. (2015) Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1. Oncogene 34:2660-71
Wen, W; Peng, C; Kim, M O et al. (2014) Knockdown of RNF2 induces apoptosis by regulating MDM2 and p53 stability. Oncogene 33:421-8
Cho, Yong-Yeon; Kim, Dong Joon; Lee, Hye Suk et al. (2013) Autophagy and cellular senescence mediated by Sox2 suppress malignancy of cancer cells. PLoS One 8:e57172
Zhang, J; Zhu, F; Li, X et al. (2012) Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. Oncogene 31:1835-44
Lee, Sung-Young; Yoon, Jaeho; Lee, Mee-Hyun et al. (2012) The role of heterodimeric AP-1 protein comprised of JunD and c-Fos proteins in hematopoiesis. J Biol Chem 287:31342-8
Peng, Cong; Zhu, Feng; Wen, Weihong et al. (2012) Tumor necrosis factor receptor-associated factor family protein 2 is a key mediator of the epidermal growth factor-induced ribosomal S6 kinase 2/cAMP-responsive element-binding protein/Fos protein signaling pathway. J Biol Chem 287:25881-92
Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun et al. (2011) Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis 32:921-8

Showing the most recent 10 out of 56 publications