The overall objective of this proposal is to characterize red ginseng extract (RGE) and its key active components (KAC) preclinically as a potent lung cancer chemopreventive agent. In a preliminary study, we demonstrated a strong efficacy of red ginseng in chemoprevention against lung tumor development in A/J mice. We hypothesize that ginseng will prevent chemically induced lung adenocarcinoma and squamous cell carcinoma formation in a mutant mouse model with genetic changes commonly seen in human lung cancers.
Four specific aims are proposed to test this hypothesis.
Aim 1 will identify the key active components of red ginseng via in vitro activity- guided fractionation chromatographic separation supplemented by measuring their intestinal absorption potentials.
Aim 2 will evaluate the effect of RGE and its KAC on lung adenocarcinoma carcinogenesis in a transgenic mouse lung adenocarcinoma model with genetic changes commonly seen in human lung cancers.
Aim 3 will determine the effect of RGE and its KAC on lung squamous cell carcinoma development in p53 mutant mice.
Aim 4 will perform pharmacokinetic and biopharmaceutical characterizations of RGE and its KAC. This proposal is timely and significant since future chemoprevention clinical trials of ginseng against lung cancer in humans require vigorous preclinical characterization of its efficacy and biopharmaceutical characteristics such as bioavailability and pharmacokinetic profile. Furthermore, we will use a newly developed mutant mouse lung tumor models of both lung adenocarcinoma and lung squamous cell carcinoma, which shares both histopathological features and genetic alterations observed in human lung carcinogenesis. The results from this proposal will provide a solid foundation for clinical trials of ginseng as a lung cancer chemopreventive agent.

Public Health Relevance

PROJECT NARRATIVE We propose to characterize red ginseng extracts (RGE) preclinically as a potent lung cancer chemopreventive agent. In vitro experiments have shown that ginseng inhibits cell proliferation and induces apoptosis in tumor cell lines. In vivo, ginseng has been shown to inhibit rodent carcinogenesis in various organ sites including the lung. We will identify the key active components of red ginseng via in vitro activity-guided fractionation chromatographic separation supplemented by measuring their intestinal absorption potentials, evaluate the effect of ginseng on lung carcinogenesis in a transgenic mouse lung carcinoma model with genetic changes commonly seen in human lung cancers, and perform pharmacokinetic and biopharmaceutical characterizations of red ginseng and its key active components. We believe that the proposed studies are significant because future chemoprevention clinical trials of ginseng against lung cancer in humans require vigorous preclinical characterization of its efficacy and biopharmaceutical characteristics such as bioavailability and pharmacokinetic profile.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT005522-04
Application #
8324234
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Williamson, John S
Project Start
2009-09-30
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$418,045
Indirect Cost
$69,390
Name
Medical College of Wisconsin
Department
Pharmacology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
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