Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.
Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.
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发表时间：
2002-12
影响因子：
5.7
通讯作者：
M. Pathak;D. Dhawan;D. Lindner;E. Borden;C. Farver;T. Yi
中科院分区：
文献类型：
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作者：
M. Pathak;D. Dhawan;D. Lindner;E. Borden;C. Farver;T. Yi
鉴于PRL家族致癌磷酸酶在人类恶性肿瘤中的潜在致病作用，它们是开发抑制物作为抗癌治疗药物的有吸引力的靶点。在此，我们证明了作用机制未知的抗原虫药物五烷双胺是一种具有抗癌潜力的PRLS抑制剂。治疗性剂量的五味子胺在体外抑制重组PRL磷酸酶，并使NIH3T3细胞异位表达的PRL失活，作用持续时间超过24小时。该药物对表达内源性催乳素的人癌细胞株具有体外生长抑制活性。在可耐受剂量下，对WM9人黑色素瘤裸鼠移植瘤的生长有明显的抑制作用，并能使癌细胞异位表达的PRL-2失活。这些观察结果提示了五烷双胺在抗癌治疗中的潜力，并可能为开发新型PTPase靶向治疗药物提供基础。
The PRL family oncogenic phosphatases are attractive targets for developing inhibitors as anticancer therapeutics given their potentially pathogenic role in human malignancies. Herein we demonstrate that pentamidine, an anti-protozoa drug with an unknown mechanism of action, is an inhibitor of PRLs with anticancer potential. Pentamidine at its therapeutic doses inhibited recombinant PRL phosphatases in vitro and inactivated ectopically expressed PRLs in NIH3T3 transfectants with an effective duration more than 24 h after a pulse cell treatment. The drug had in vitro growth-inhibitory activity against human cancer cell lines that express the endogenous PRLs. Pentamidine at a tolerable dose markedly inhibited the growth of WM9 human melanoma tumors in nude mice coincident with the induction of tumor cell necrosis and is capable of inactivating ectopically expressed PRL-2 in the cancer cells. These observations suggest the potential of pentamidine in anticancer therapies and may provide a basis for developing novel PTPase-targeted therapeutics.