Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4627-30. doi: 10.1016/j.bmcl.2010.06.003. Epub 2010 Jun 8.
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.
越来越多的证据表明,趋化因子受体 CCR5 和趋化因子 CCL5 可能参与了前列腺癌的增殖和转移。因此,趋化因子受体 CCR5 拮抗剂可能作为抗前列腺癌药物发挥作用。作为第一个天然产物 CCR5 拮抗剂,阿尼巴胺与通过高通量筛选鉴定的其他已知拮抗剂相比,提供了一个新的化学结构骨架。我们的研究表明,阿尼巴胺在微摩尔至亚微摩尔浓度下对前列腺癌细胞增殖具有显著的抑制作用,并抑制高转移性 M12 前列腺癌细胞系的黏附和侵袭。初步体内研究表明,阿尼巴胺也能抑制小鼠前列腺肿瘤的生长。这些发现表明,阿尼巴胺可能成为开发前列腺癌治疗药物的新型先导化合物。