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Abstract

Grant Number:	5R21AT001539-02
Project Title:	Therapeutic effect of boswellin in prostate cancer

PI Information:	Name	Email	Title
	JING, YONGKUI	yongkui.jing@mssm.edu

Abstract: DESCRIPTION (provided by applicant): Prostate cancer is the second leading cause of male death in the United States. The current adjuvant treatment modalities for prostate cancer, hormone ablation and endocrine therapy, often lead to temporary gains, which are followed by disease relapse within as little as 1-2 years post-treatment. Therefore, there is a pressing need to identify molecular targets, which may lead to longer-lived gains in disease management. Prostate cancers have been shown to over express 5-lipoxygenase (5-LOX). 5-hydroxyeicosatetraenoic acid (5-HETE) and 5-oxo-6E, SZ, 11Z, 14Z-eicosatetraenoic acid (5-oxETE), the products of 5-LOX, have been found to be cell survival factors and blocking the synthesis of these products leads to cell apoptosis. Thus 5-LOX is a potential molecular target for prostate cancer treatment. We have found that prostate cancer cells are sensitive to boswellic acid (a pure 5-LOX inhibitor isolated from Boswellia carterri and serrata) -induced cell growth inhibition and apoptosis. Boswellin, a crude methanol extract containing 20% boswellic acids, is currently used as a complementary anti-arthritic and anti-inflammatory pharmacological agent in the US. We hypothesize that prostate cancer will be highly sensitive to Boswellin-induced growth inhibition via apoptosis. We propose 1) to investigate cell growth inhibition and apoptosis induction by Boswellin and its ingredients among prostate cancer cells and normal prostate epithelial cells. The connection between Boswellin-induced apoptosis and 5-LOX inhibition will be tested by comparing 5-LOX activity and cell sensitivity to Boswellin-induced growth inhibition. 2) To determine the efficacy of Boswellin in preclinical animal models. Acute and subchronic toxicity will be tested in mice and rats, respectively. Tumor growth inhibition and apoptosis induction will then be measured using doses determined not to cause untolerable toxicity. We hope our proposal will lead to the discovery of a novel complementary agent for prostate cancer treatment.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
antiinflammatory agent, apoptosis, cell growth regulation, lipoxygenase, neoplasm /cancer chemotherapy, oxidoreductase inhibitor, plant extract, prostate neoplasm
cytotoxicity, enzyme activity, nonhuman therapy evaluation, pharmacokinetics
athymic mouse, laboratory rat, neoplastic cell, terminal nick end labeling, tissue /cell culture, xenotransplantation

Institution:	MOUNT SINAI SCHOOL OF MEDICINE OF NYU
	OF NEW YORK UNIVERSITY
	NEW YORK, NY 100296574
Fiscal Year:	2005
Department:	MEDICINE
Project Start:	01-JAN-2004
Project End:	30-NOV-2006
ICD:	NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE
IRG:	ZAT1

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