Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer.

Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Research Abstract Details 

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Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Abstract Text:

Ahmed O Kaseb,Kannagi Chinnakannu,Di Chen,Arun Sivanandam,Sheela Tejwani,Mani Menon,Q Ping Dou,G Prem-Veer Reddy,

Relapse of prostate cancer after androgen ablation therapy is hormone-refractory, with continued tumor growth being dependent on the androgen receptor (AR). E2F-1, a regulator of cell proliferation and viability, reportedly plays a role in the development of hormone-refractory prostate cancer. Thymoquinone is a component of Nigella sativa, an herb used for thousands of years for culinary and medicinal purposes in Asian and Middle Eastern countries and has been reported to have an antineoplastic effect both in vitro and in vivo. We observed that thymoquinone inhibited DNA synthesis, proliferation, and viability of cancerous (LNCaP, C4-B, DU145, and PC-3) but not noncancerous (BPH-1) prostate epithelial cells by down-regulating AR and E2F-1. In LNCaP cells, this was associated with a dramatic increase in p21(Cip1), p27(Kip1), and Bax. Thymoquinone blunted progression of synchronized LNCaP cells from G1 to S phase, with a concomitant decrease in AR and E2F-1 as well as the E2F-1-regulated proteins necessary for cell cycle progression. In a xenograft prostate tumor model, thymoquinone inhibited growth of C4-2B-derived tumors in nude mice. This in vivo suppression of tumor growth, as with C4-2B cell growth in culture, was associated with a dramatic decrease in AR, E2F-1, and cyclin A as determined by Western blot of tissue extracts. Tissue immunohistochemical staining confirmed a marked reduction in E2F-1 and showed induction of apoptosis on terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay. These findings show that thymoquinone suppresses the expression of AR and E2F-1 necessary for proliferation and viability of androgen-sensitive as well as androgen-independent prostate cancer cells both in vitro and in vivo and, moreover, produced no noticeable side effects in mice. We conclude that thymoquinone, a naturally occurring herbal product, may prove to be effective in treating hormone-sensitive as well as hormone-refractory prostate cancer. Furthermore, because of its selective effect on cancer cells, we believe that thymoquinone can also be used safely to help prevent the development of prostate cancer.

Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Publishing Authors By Initials

AO Kaseb,K Chinnakannu,D Chen,A Sivanandam,S Tejwani,M Menon,QP Dou,GP Reddy,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 7782-8

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Aug

YEAR: 2007

Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: drug effects

Chemical & Substance for Abstract: Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Information

Substance Name: thymoquinone

Registry Number: 490-91-5

Grant and Affiliation Information for Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer.

AFFILIATION: Department of Hematology/Oncology, Henry Ford Hospital, MI 458202, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK57864

ACRONYM: DK

MEDLINETA: Cancer Res

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