Colorectal cancer is a leading cause of cancer-related death in the United States. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of colorectal cancer. The candidate, Dr. Chong-Zhi Wang, is an experienced phytochemical scientist at University of Chicago. This application describes a development award for Dr. Wang, to successfully achieve his long-term career goals of obtaining the skills necessary to become an independent investigator in biomedical research, concentrating on the efficacy and mechanism of bioactive botanical extracts/compounds for treating colorectal cancer. Training for Dr. Wang will focus on advancing his knowledge of pharmacognosy and metabolism of phytoconstituents, understanding cancer pathophysiology, becoming proficient in biostatistics knowledge, and improving his grant writing ability. The advisory team is composed of senior experts from the University of Chicago and University of Illinois at Chicago. The Primary Mentor Dr. Chun-Su Yuan, a Principal Investigator of NIH Center for Botanical Research on Colorectal Cancer at University of Chicago, will closely direct Dr. Wang's training and research. Preliminary data showed that the different fractions from Scutellaria baicalensis extract (SbE) had opposing effects on human colorectal cancer cells. The hypothesis of this study is that if the baicalin and scutellarein, hydrophilic constituents, are removed from S. baicalensis extract or transformed into lipophilic constituents, the anticancer effects of the extract will increase significantly. The purpose of the research is to develop a new process for preparing an aglycon-rich fraction (ARF) of S. baicalensis extract in improving its anticancer activities and to elucidate the underlying mechanisms.
The specific aims are as follows:
Aim 1. Authentication, extraction and isolation of SbE and preparation of ARF.
Aim 2. Evaluation of the effects of SbE and ARF on colorectal cancer and related mechanisms of action.
Aim 3. Further investigation of ARF-induced apoptotic pathways. Data from this proposed study will have the potential to advance cancer treatment regimens, and improve the quality of life for patients suffering from colorectal cancer. Upon successful completion of this award, Dr. Wang will be fully prepared for his independent investigation of additional pharmacologically based studies using phytoconstituents against colorectal cancer.

Public Health Relevance

Colorectal cancer is a leading cause of cancer related death in the United States. While advances have been made in developing effective treatment strategies for this cancer, chemotherapies are still limited by severe adverse effects and dose-limiting toxicity. This Project will use Scutellaria baicalensis, a Chinese herb medicine, with a new extract process to produce an active fraction, and evaluate the active fraction's anticancer effects on colorectal cancer.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AT005362-03
Application #
8233477
Study Section
Special Emphasis Panel (ZAT1-PK (09))
Program Officer
Williamson, John S
Project Start
2010-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$98,231
Indirect Cost
$7,276
Name
University of Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Zhang, Zhiyu; Yu, Chunhao; Zhang, Chun-Feng et al. (2014) Chemopreventive effects of oplopantriol A, a novel compound isolated from Oplopanax horridus, on colorectal cancer. Nutrients 6:2668-80
Yu, Chunhao; Wang, Chong-Zhi; Zhou, Chun-Jie et al. (2014) Adulteration and cultivation region identification of American ginseng using HPLC coupled with multivariate analysis. J Pharm Biomed Anal 99:8-15
Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao et al. (2014) Panax notoginseng attenuates experimental colitis in the azoxymethane/dextran sulfate sodium mouse model. Phytother Res 28:892-8
Huang, Wei-Hua; Shao, Li; Wang, Chong-Zhi et al. (2014) Anticancer activities of polyynes from the root bark of Oplopanax horridus and their acetylated derivatives. Molecules 19:6142-62
Huang, Wei-Hua; Zhang, Qing-Wen; Yuan, Chun-Su et al. (2014) Chemical constituents of the plants from the genus Oplopanax. Chem Biodivers 11:181-96
Ueno, Nobuhiro; Hasebe, Takumu; Kaneko, Atsushi et al. (2014) TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-?B suppression. PLoS One 9:e97456
Tung, Nguyen Huu; Du, Guang-Jian; Yuan, Chun-Su et al. (2013) Isolation and chemopreventive evaluation of novel naphthoquinone compounds from Alkanna tinctoria. Anticancer Drugs 24:1058-68
Yu, Chunhao; Qu, Fengyun; Mao, Yanyong et al. (2013) Different extraction pretreatments significantly change the flavonoid contents of Scutellaria baicalensis. Pharm Biol 51:1228-35
Wang, Chong-Zhi; Li, Binghui; Wen, Xiao-Dong et al. (2013) Paraptosis and NF-*B activation are associated with protopanaxadiol-induced cancer chemoprevention. BMC Complement Altern Med 13:2
Zhang, Zhiyu; Wang, Chong-Zhi; Wen, Xiao-Dong et al. (2013) Role of saffron and its constituents on cancer chemoprevention. Pharm Biol 51:920-4

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