Singh Parminder, Rathinasamy Krishnan, Mohan Renu, Panda Dulal
School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
IUBMB Life. 2008 Jun;60(6):368-75. doi: 10.1002/iub.42.
Microtubules, composed of alphabeta tubulin dimers, are dynamic polymers of eukaryotic cells. They play important roles in various cellular functions including mitosis. Microtubules exhibit differential dynamic behaviors during different phases of the cell cycle. Inhibition of the microtubule assembly dynamics causes cell cycle arrest leading to apoptosis; thus, qualifying them as important drug targets for treating several diseases including cancer, neuronal, fungal, and parasitic diseases. Although several microtubule-targeted drugs are successfully being used in cancer chemotherapy, the development of resistance against these drugs and their inherent toxicities warrant the development of new agents with improved efficacy. Several antimicrotubule agents are currently being evaluated for their possible uses in cancer chemotherapy. Benomyl, griseofulvin, and sulfonamides have been used as antifungal and antibacterial drugs. Recent reports have shown that these drugs have potent antitumor potential. These agents are shown to inhibit proliferation of different types of tumor cells and induce apoptosis by targeting microtubule assembly dynamics. However, unlike vincas and taxanes, which inhibit cancer cell proliferation in nanomolar concentration range, these agents act in micromolar range and are considered to have limited toxicities. Here, we suggest that these drugs may have a significant use in cancer chemotherapy when used in combination with other anticancer drugs.
微管由αβ微管蛋白二聚体组成,是真核细胞的动态聚合物。它们在包括有丝分裂在内的各种细胞功能中发挥重要作用。微管在细胞周期的不同阶段表现出不同的动态行为。抑制微管组装动态会导致细胞周期停滞,进而引发凋亡;因此,微管成为治疗包括癌症、神经疾病、真菌疾病和寄生虫疾病在内的多种疾病的重要药物靶点。尽管几种微管靶向药物已成功用于癌症化疗,但对这些药物的耐药性发展及其固有的毒性促使人们研发疗效更佳的新型药物。目前正在评估几种抗微管药物在癌症化疗中的潜在用途。苯菌灵、灰黄霉素和磺胺类药物已用作抗真菌和抗菌药物。最近的报告表明,这些药物具有强大的抗肿瘤潜力。这些药物显示出通过靶向微管组装动态来抑制不同类型肿瘤细胞的增殖并诱导凋亡。然而,与在纳摩尔浓度范围内抑制癌细胞增殖的长春花生物碱和紫杉烷不同,这些药物在微摩尔范围内起作用,且被认为毒性有限。在此,我们认为这些药物与其他抗癌药物联合使用时,可能在癌症化疗中具有重要用途。