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 #
5R01CA111536-05
Application #
7617116
Study Section
Special Emphasis Panel (ZRG1-CDP (01))
Program Officer
Malone, Winfred F
Project Start
2005-06-30
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
5
Fiscal Year
2009
Total Cost
$282,772
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
Lee, Dong Eun; Lee, Ki Won; Jung, Sung Keun et al. (2011) 6,7,4'-trihydroxyisoflavone inhibits HCT-116 human colon cancer cell proliferation by targeting CDK1 and CDK2. Carcinogenesis 32:629-35

Showing the most recent 10 out of 56 publications