The overall objective of this renewal application remains to discover novel chemopreventive agents derived from the natural products. This project will continue to utilize mammary gland organ culture and in vivo carcinogenesis models (skin and mammary) to evaluate biological effectiveness of potential chemopreventive agents identified in the initial screen. As indicated in the theme of this program, extracts or fractions considered as active leads will be first evaluated for its chemopreventive activity against 7,12, dimethylbenz(a)anthracene (DMBA) induced mammary lesions in organ cultures. If the exact shows dramatic activity in the culture system, it will be evaluated against two stage skin carcinogenesis model. Some extracts or isolated fractions will be further characterized and again their activity will be assessed. The newly identified agent which is considered active is again evaluated against mammary lesion formation. The active compound is then synthesized and carcinogenesis studies will be initiated. Brassinin and the extract of Mundulea sericea (P00053) were selected for the carcinogenesis experiments based on the results from the in vitro assays and organ culture experiments (this project). These studies have shown excellent inhibition against skin carcinogenesis. In addition we propose to conduct studies to evaluate activity of newly identified chemopreventive agent for its activity either as an anti-initiator or as an anti-promoter in organ cultures. This will allow us to design in vivo studies to confirm such stage specific effects and to understand the mechanism of action of these agents. A variety of other carcinogenesis models have been established in our laboratory for assessing chemopreventive potential at other target organs, and they will be used as required. In summary, this project will serve to provide a definite biological end point for newly identified potential chemopreventive agents in this program project.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA048112-07S1
Application #
6295983
Study Section
Project Start
1997-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Youn, Ui Joung; Sripisut, Tawanun; Park, Eun-Jung et al. (2015) Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum. Bioorg Med Chem Lett 25:4719-23
Chai, Xingyun; Youn, Ui Joung; Sun, Dianqing et al. (2014) Herbicidin congeners, undecose nucleosides from an organic extract of Streptomyces sp. L-9-10. J Nat Prod 77:227-33
Ihsan-ul-Haq; Mirza, Bushra; Kondratyuk, Tamara P et al. (2013) Preliminary evaluation for cancer chemopreventive and cytotoxic potential of naturally growing ethnobotanically selected plants of Pakistan. Pharm Biol 51:316-28
Ihsan-ul-Haq; Youn, Ui Joung; Chai, Xingyun et al. (2013) Biologically active withanolides from Withania coagulans. J Nat Prod 76:22-8
St John, Sarah E; Jensen, Katherine C; Kang, Soosung et al. (2013) Design, synthesis, biological and structural evaluation of functionalized resveratrol analogues as inhibitors of quinone reductase 2. Bioorg Med Chem 21:6022-37
Conda-Sheridan, Martin; Park, Eun-Jung; Beck, Daniel E et al. (2013) Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential. J Med Chem 56:2581-605
Park, Eun-Jung; Pezzuto, John M; Jang, Kyoung Hwa et al. (2012) Suppression of nitric oxide synthase by thienodolin in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells. Nat Prod Commun 7:789-94
Kondratyuk, Tamara P; Park, Eun-Jung; Yu, Rui et al. (2012) Novel marine phenazines as potential cancer chemopreventive and anti-inflammatory agents. Mar Drugs 10:451-64
Reddy, P V Narasimha; Jensen, Katherine C; Mesecar, Andrew D et al. (2012) Design, synthesis, and biological evaluation of potent quinoline and pyrroloquinoline ammosamide analogues as inhibitors of quinone reductase 2. J Med Chem 55:367-77
Mayhoub, Abdelrahman S; Marler, Laura; Kondratyuk, Tamara P et al. (2012) Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets. Bioorg Med Chem 20:510-20

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