Prostate cancer is the most commonly diagnosed malignancy in American men and the second leading cause of cancer death in men. Androgen deprivation therapy has been the standard treatment against hormone-dependent prostate cancer; unfortunately, androgen-independent cells usually emerge after a few years of androgen ablation therapy. Chemotherapy is often palliative at this stage, but it does not significantly increase the life span of prostate cancer patients. Because of this situation, many prostate cancer patients turn to alternative therapies to treat their disease, often without informing their physicians. In this proposal, two currently popular herbal preparations, green tea extracts and PC-SPES will be analyzed for their potential to affect the response of prostate cancer at different stages of progression to hormonal interventions, including androgens, anti-androgens, estrogens and inhibitors of 5(alpha)-reductase. In the first aim, it will be determined if green tea extracts and PC-SPES (and extracts of individual component herbs) affect the ability of androgens, anti-androgens and 5(alpha)-reductase inhibitors to control cell cycle processes and the growth of human prostate cancer LNCaP cells representing different stages of prostate cancer progression in culture and as tumor xenografts in athymic nude mice. In the second aim, it will be determined if green tea extracts and PC-SPES (and extracts of individual component herbs) affect the chemotherapeutic effects of epigallocatechin gallate on human prostate LNCaP cancer cells/tumors representing different stages of prostate cancer progression, in culture and in athymic mice. In the third aim, it will be determined if PC-SPES modulates the effects of estrogens and if estrogenic components of PC-SPES are responsible for effects on the cell cycle and the growth of prostate cancer cells representing different stages of prostate cancer progression in culture and in athymic mice.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
1R01AT000850-01
Application #
6411783
Study Section
Special Emphasis Panel (ZAT1-C (11))
Program Officer
West, Neal B
Project Start
2001-09-12
Project End
2004-05-31
Budget Start
2001-09-12
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$374,000
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Peng, Dacheng; Hiipakka, Richard A; Xie, Jing-Tian et al. (2011) A novel potent synthetic steroidal liver X receptor agonist lowers plasma cholesterol and triglycerides and reduces atherosclerosis in LDLR(-/-) mice. Br J Pharmacol 162:1792-804
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Chuu, Chih-Pin; Chen, Rou-Yu; Kokontis, John M et al. (2009) Suppression of androgen receptor signaling and prostate specific antigen expression by (-)-epigallocatechin-3-gallate in different progression stages of LNCaP prostate cancer cells. Cancer Lett 275:86-92
Peng, Dacheng; Hiipakka, Richard A; Reardon, Catherine A et al. (2009) Differential anti-atherosclerotic effects in the innominate artery and aortic sinus by the liver X receptor agonist T0901317. Atherosclerosis 203:59-66
Peng, Dacheng; Hiipakka, Richard A; Dai, Qing et al. (2008) Antiatherosclerotic effects of a novel synthetic tissue-selective steroidal liver X receptor agonist in low-density lipoprotein receptor-deficient mice. J Pharmacol Exp Ther 327:332-42
Chuu, Chih-Pin; Chen, Rou-Yu; Hiipakka, Richard A et al. (2007) The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells. Biochem Biophys Res Commun 357:341-6
Chuu, Chih-pin; Hiipakka, Richard A; Kokontis, John M et al. (2006) Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist. Cancer Res 66:6482-6
Fukuchi, Junichi; Song, Ching; Dai, Qing et al. (2005) 5beta-Cholane activators of the farnesol X receptor. J Steroid Biochem Mol Biol 94:311-8
Kokontis, John M; Hsu, Stephen; Chuu, Chih-pin et al. (2005) Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity. Prostate 65:287-98

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