Microtubule assembly dynamics: an attractive target for anticancer drugs.
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.
Singh
Parminder
P
School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Rathinasamy
Krishnan
K
Mohan
Renu
R
Panda
Dulal
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001542:Benomyl / Q000494:pharmacology; D006118:Griseofulvin / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D011487:Protein Conformation; D013449:Sulfonamides / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry*; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D013449:Sulfonamides; D014404:Tubulin; D006118:Griseofulvin; D014747:Vinblastine; D017239:Paclitaxel; D001542:Benomyl