Male contraceptive Adjudin is a potential anti-cancer drug.
Male contraceptive Adjudin is a potential anti-cancer drug.
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DOI：
10.1016/j.bcp.2012.11.008
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
Xia, Weiliang
中科院分区：
文献类型：
--
作者：
Xie, Qian Reuben;Liu, Yewei;Shao, Jiaxiang;Yang, Jian;Liu, Tengyuan;Zhang, Tingting;Wang, Boshi;Mruk, Dolores D.;Silvestrini, Bruno;Cheng, C. Yan;Xia, Weiliang
Adjudin，也称为AF-2364和氯尼达明（LND）的类似物，是一种雄性避孕药，当口服给药于成年大鼠、兔或犬时，通过诱导生精上皮中的精子过早耗竭发挥作用。还已知LND可以靶向线粒体并阻断肿瘤细胞中的能量代谢。然而，Adjudin是否具有任何抗癌活性仍有待阐明。在本文中，我们描述了Adjudin对体外癌细胞和接种在裸鼠中的肺和前列腺肿瘤的抗增殖活性。我们发现Adjudin通过Caspase-3依赖性途径诱导癌细胞凋亡。进一步的实验表明，Adjudin可以触发癌细胞中的线粒体功能障碍，明显影响线粒体质量，诱导线粒体膜电位的丧失和降低细胞ATP水平。Adjudin对荷瘤裸鼠的腹腔给药也显著抑制了肺和前列腺肿瘤的生长。当与顺铂联合使用时，Adjudin增强了对顺铂诱导的癌细胞毒性的敏感性。综上所述，这些发现表明Adjudin可能是一种潜在的癌症治疗药物。
Adjudin, also known as AF-2364 and an analog of lonidamine (LND), is a male contraceptive acting through the induction of premature sperm depletion from the seminiferous epithelium when orally administered to adult rats, rabbits or dogs. It is also known that LND can target mitochondria and block energy metabolism in tumor cells. However, whether Adjudin exhibits any anti-cancer activity remains to be elucidated. Herein we described the anti-proliferative activity of Adjudin on cancer cells in vitro and on lung and prostate tumors inoculated in nude mice. We found that Adjudin induced apoptosis in cancer cells through a Caspase-3-dependent pathway. Further experiments revealed that Adjudin could trigger mitochondrial dysfunction in cancer cells, apparently affecting the mitochondrial mass, inducing the loss of mitochondrial membrane potential and reducing cellular ATP levels. Intraperitoneal administration of Adjudin to tumor-bearing athymic nude mice also significantly suppressed the lung and prostate tumor growth. When used in combination with cisplatin, Adjudin enhances the sensitivity to cisplatin-induced cancer cell cytotoxicity. Taken together, these findings have demonstrated that Adjudin may be a potential drug for cancer therapy.
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