Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways.
Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways.
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DOI：
10.1038/s41598-018-30158-6
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发表时间：
2018-08-09
影响因子：
4.6
通讯作者：
Mukhopadhyay T
中科院分区：
文献类型：
--
作者：
Dogra N;Kumar A;Mukhopadhyay T
已经临床批准或实验测试用于癌症以外的条件的药物，但被发现具有以前未被识别的对恶性细胞的细胞毒性，可以作为合适的抗癌候选药物。N-（6-苯硫基-1H-苯并咪唑-2-基）氨基甲酸甲酯[Fenbendazole，FZ]是一种苯并咪唑类化合物，是一种安全、廉价的驱虫药，具有高效的抗增殖活性。在我们早期的工作中，我们报道了一个强大的生长抑制活性的FZ引起的部分蛋白酶体功能受损。在这里，我们表明，FZ表现出中等亲和力的哺乳动物微管蛋白和发挥细胞毒性的人类癌细胞在微摩尔浓度。同时，它引起线粒体p53易位，并有效地抑制葡萄糖摄取，GLUT转运蛋白的表达以及己糖激酶（HK II）-一种大多数癌细胞赖以生存的关键糖酵解酶。结合我们早期的数据，结果表明，FZ是一种新的微管干扰剂，显示抗肿瘤活性，并可能被评估为潜在的治疗剂，因为它对多种细胞途径的影响，导致有效消除癌细胞。
Drugs that are already clinically approved or experimentally tested for conditions other than cancer, but are found to possess previously unrecognized cytotoxicity towards malignant cells, may serve as fitting anti-cancer candidates. Methyl N-(6-phenylsulfanyl-1H benzimidazol-2-yl) carbamate [Fenbendazole, FZ], a benzimidazole compound, is a safe and inexpensive anthelmintic drug possessing an efficient anti-proliferative activity. In our earlier work, we reported a potent growth-inhibitory activity of FZ caused partially by impairment of proteasomal function. Here, we show that FZ demonstrates moderate affinity for mammalian tubulin and exerts cytotoxicity to human cancer cells at micromolar concentrations. Simultaneously, it caused mitochondrial translocation of p53 and effectively inhibited glucose uptake, expression of GLUT transporters as well as hexokinase (HK II) - a key glycolytic enzyme that most cancer cells thrive on. It blocked the growth of human xenografts in nu/nu mice model when mice were fed with the drug orally. The results, in conjunction with our earlier data, suggest that FZ is a new microtubule interfering agent that displays anti-neoplastic activity and may be evaluated as a potential therapeutic agent because of its effect on multiple cellular pathways leading to effective elimination of cancer cells.
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影响因子：
4.8
作者：
Giustiniani, Julien;Daire, Vanessa;Baillet, Anita
通讯作者：
Baillet, Anita
影响因子：
5.2
作者：
Barbuti AM;Chen ZS
通讯作者：
Chen ZS
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William
DOI：
10.1073/pnas.132275599
发表时间：
2002-08-06
影响因子：
11.1
作者：
Giannakakou, P;Nakano, M;Fojo, T
通讯作者：
Fojo, T
DOI：
10.2174/1568011023354290
发表时间：
2002-01-01
期刊：
Current Medicinal Chemistry - Anti-Cancer Agents
影响因子：
--
作者：
Jordan, M. A.
通讯作者：
Jordan, M. A.