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Grant Abstract

Grant Number: 5R21AT001535-02
PI Name: HARRIS, DIANE M.
Project Title: Scutellaria baicalensis and Colon Cancer Chemoprevention

Abstract: DESCRIPTION (provided by applicant) The use of herbal medicines among patients who are at risk for developing cancer or patients with cancer is an increasingly popular approach. There exists a large body of anecdotal knowledge on the use of herbals, however the precise cellular and tissue targets of herbal mixtures, as well as the active ingredients and their mechanisms of action, are still poorly defined. Additionally, there is accumulating evidence that the complex mixture of compounds found in many herbal products may have increased efficacy and decreased toxicity over using the single isolated compound in a pharmaceutical-like approach. In vitro cell culture models are useful for isolating specific mechanisms of action in a tightly controlled system and for screening compounds for specific actions. Use of an in vivo model to study efficacy of herbals is complementary to in vitro systems, as use of a whole animal system more closely simulates human intake of the herbals. The overall goal of the studies proposed here is to evaluate Scutellaria baicalensis for its chemopreventive properties both in cell culture using a panel of colon cancer lines and in the Apcmin mouse model of intestinal cancer. The extract of Scutellaria baicalensis (Baikal or Chinese skullcap) was chosen as a potential cancer preventive agent based on previous demonstration of anti-inflammatory action and its effectiveness as part of several mixed botanical medicines with anti-cancer properties, including PC-SPES. We plan to compare the complex extract of Scutellaria to one of the active ingredients, baicalin, in order to demonstrate that the mixture has greater efficacy than the isolated compound. Effects on proliferation, cell cycling, apoptosis, and arachidonic acid metabolism will be determined in vitro and effects on polyp formation in the Apcmin mouse model will be evaluated in vivo. In addition, we will test the bioavailability of baicalin in the crude extract in comparison to that of the compound administered alone in wild-type mice. Results from these studies will provide further evidence of efficacy of Scutellaria baicalensis extracts and the bioactive compound baicalin in intestinal cancer and provide rationale for further testing in clinical studies in patients with colon cancer as possible adjunct therapy and in at-risk patients for prevention.

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