This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yi, T. Articles by Liu, M. PubMed PubMed Citation Articles by Yi, T. Articles by Liu, M.

Research Articles: Therapeutics, Targets, and Development

Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways

¹ Center for Cancer and Stem Cell Biology, Institute for Bioscience and Technology, Texas A&M University System Health Science Center; ² Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and ³ Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, People's Republic of China

Requests for reprints: Mingyao Liu, Center for Cancer and Stem Cell Biology, Institute for Bioscience and Technology, Texas A&M University System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030. Phone: 713-677-7505; Fax: 713-677-7512. E-mail: mliu{at}ibt.tamhsc.edu

Abstract

Thymoquinone, a component derived from the medial plant Nigella sativa, has been used for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on cell proliferation of many cancer cell lines and hormone-refractory prostate cancer by suppressing androgen receptor and E2F-1. Whether thymoquinone inhibits tumor angiogenesis, the critical step of tumor growth and metastasis, is still unknown. In this study, we found that thymoquinone effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation. Thymoquinone inhibited cell proliferation and suppressed the activation of AKT and extracellular signal-regulated kinase. Thymoquinone blocked angiogenesis in vitro and in vivo, prevented tumor angiogenesis in a xenograft human prostate cancer (PC3) model in mouse, and inhibited human prostate tumor growth at low dosage with almost no chemotoxic side effects. Furthermore, we observed that endothelial cells were more sensitive to thymoquinone-induced cell apoptosis, cell proliferation, and migration inhibition compared with PC3 cancer cells. Thymoquinone inhibited vascular endothelial growth factor–induced extracellular signal-regulated kinase activation but showed no inhibitory effects on vascular endothelial growth factor receptor 2 activation. Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth and could be used as a potential drug candidate for cancer therapy. [Mol Cancer Ther 2008;7(7):1789–96]

Grant support: National Cancer Institute/NIH grant 1R01CA106479 (M. Liu).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: T. Yi, S-G. Cho, and Z. Yi contribute equally to this work.

Received 2/ 4/08; revised 4/12/08; accepted 4/18/08.