Anibamine,a natural product CCR5 antagonist,as a novel lead for the development of anti-prostate cancer agents |
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| Authors: | Xueping Zhang Kendra M Haney Amanda C Richardson Eden Wilson David A Gewirtz Joy L Ware Zendra E Zehner Yan Zhang |
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| Institution: | 1. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA;2. Department of Medicinal Chemistry, Virginia Commonwealth University, 800 East Leigh Street, PO Box 980540, Richmond, VA 23298-0540, USA;3. Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA;4. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA;5. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA |
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| Abstract: | Accumulating evidence indicates that the chemokine receptor CCR5 and the chemokine CCL5 may be involved in the proliferation and metastasis of prostate cancer. Consequently, chemokine receptor CCR5 antagonists could potentially act as anti-prostate cancer agents. As the first natural product CCR5 antagonist, anibamine provides a novel chemical structural skeleton compared with other known antagonists identified through high-throughput screening. Our studies demonstrate that anibamine produces significant inhibition of prostate cancer cell proliferation at micromolar to submicromolar concentrations as well as suppressing adhesion and invasion of the highly metastatic M12 prostate cancer cell line. Preliminary in vivo studies indicate that anibamine also inhibits prostate tumor growth in mice. These findings indicate that anibamine may prove to be a novel lead compound for the development of prostate cancer therapeutic agents. |
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