Nocodazole (CAS 31430-18-9)

Nocodazole is an anti-neoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules (tubulin). Several drugs including vincristine and colcemid are similar to Nocodazole in that they interfere with microtubule polymerization. As Nocodazole affects the cytoskeleton, it is often employed in cell biology experiments as a control: for example, some dominant negative Rho small GTPases cause a similar effect as Nocodazole, and constitutively activated mutants often reverse or negate the effect. Nocodazole is frequently employed in cell biology laboratories to synchronize the cell division cycle. Cells treated with Nocodazole arrest with a G2- or M-phase DNA content when analyzed by flow cytometry. Nocodazole binds to the same site as colchinine on beta-tubulin to inhibit microtubule polymerization. But, unlike colchicine, the effects of Nocodazole are reversible. Microscopy of Nocodazole-treated cells shows that they do enter mitosis but cannot form metaphase spindles because microtubules (of which the spindles are made) cannot polymerize. The absence of microtubule attachment to kinetochores activates the spindle assembly checkpoint, causing the cell to arrest in prometaphase. For cell synchronization experiments, Nocodazole is usually employed at a concentration of 40-100 ng/mL of culture medium for a duration of 12-18 hours. Prolonged arrest of cells in mitosis due to Nocodazole treatment typically results in apoptosis. Another standard cell biological application of Nocodazole is to induce the formation of Golgi ministacks in eukaryotic cells. The perinuclear structural organization of the Golgi apparatus in eukaryotes is dependent on microtubule trafficking, but disrupting the trafficking of Golgi elements from the endoplasmic reticulum treatment with Nocodazole (33 uM for 3 hours works) induces numerous Golgi elements to form adjacent to ER exit sites. These functional Golgi ministacks remain distributed about the cell, unable to track forward to form a perinuclear Golgi since Nocodazole has depolymerized the microtubules. Nocodazole is also known as Oncodazole, NSC 238159, R 17934, and Methyl-[5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]-carbamate.

Referencias

1. Nocodazole inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes via a microtubule-independent mechanism.  |  Molero, JC., et al. 2001. J Biol Chem. 276: 43829-35. PMID: 11571289
2. Interaction of oncodazole (R 17934), a new antitumoral drug, with rat brain tubulin.  |  Hoebeke, J., et al. 1976. Biochem Biophys Res Commun. 69: 319-24. PMID: 1267789
3. Nocodazole does not synchronize cells: implications for cell-cycle control and whole-culture synchronization.  |  Cooper, S., et al. 2006. Cell Tissue Res. 324: 237-42. PMID: 16432713
4. Nocodazole delays viral entry into the brain following footpad inoculation with West Nile virus in mice.  |  Hunsperger, EA. and Roehrig, JT. 2009. J Neurovirol. 15: 211-8. PMID: 19444694
5. Nocodazole induces mitotic cell death with apoptotic-like features in Saccharomyces cerevisiae.  |  Endo, K., et al. 2010. FEBS Lett. 584: 2387-92. PMID: 20399776
6. Nocodazole treatment decreases expression of pluripotency markers Nanog and Oct4 in human embryonic stem cells.  |  Kallas, A., et al. 2011. PLoS One. 6: e19114. PMID: 21559451
7. Nocodazole increases the ERK activity to enhance MKP-1expression which inhibits p38 activation induced by TNF- alpha .  |  Guo, X., et al. 2012. Mol Cell Biochem. 364: 373-80. PMID: 22294037
8. Dominant lethal effects of nocodazole in germ cells of male mice.  |  Attia, SM., et al. 2015. Food Chem Toxicol. 77: 101-4. PMID: 25595372
9. Nocodazole Induced Suicidal Death of Human Erythrocytes.  |  Signoretto, E., et al. 2016. Cell Physiol Biochem. 38: 379-92. PMID: 26824457
10. Nocodazole treatment interrupted Brucella abortus invasion in RAW 264.7 cells, and successfully attenuated splenic proliferation with enhanced inflammatory response in mice.  |  Reyes, AW., et al. 2017. Microb Pathog. 103: 87-93. PMID: 28017899
11. Nocodazole-Induced Expression and Phosphorylation of Anillin and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin.  |  Douglas, P., et al. 2020. Mol Cell Biol. 40: PMID: 32284347
12. Theoretical study of the geometric and electronic characterization of carbendazim-based drug (Nocodazole).  |  Khattab, M. 2020. Heliyon. 6: e04055. PMID: 32548318
13. Synchronization of human retinal pigment epithelial-1 cells in mitosis.  |  Scott, SJ., et al. 2020. J Cell Sci. 133: PMID: 32878943
14. Revisiting Activity of Some Nocodazole Analogues as a Potential Anticancer Drugs Using Molecular Docking and DFT Calculations.  |  Khattab, M. and Al-Karmalawy, AA. 2021. Front Chem. 9: 628398. PMID: 33842429
15. Optimizing Cell Synchronization Using Nocodazole or Double Thymidine Block.  |  Surani, AA., et al. 2021. Methods Mol Biol. 2329: 111-121. PMID: 34085219