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The structure of paclitaxel, a widely used mitotic inhibitor.

A mitotic inhibitor is a type of drug derived from natural substances such as plant alkaloids and primarily used in cancer treatment and certain types of cancer research including cytogenetics.[1] Cancer cells are able to grow and eventually metastasize through continuous mitotic division. Generally speaking, mitotic inhibitors prevent cells from undergoing mitosis by disrupting microtubule polymerization, thus preventing cancerous growth. Mitotic inhibitors work by interfering with and halting mitosis (usually during the M phase of the cell cycle), so that the cell will no longer divide.[2] Tubulin, a necessary protein for mitosis to occur, is suppressed by the mitotic inhibitor, preventing mitosis altogether.[3]

Examples of mitotic inhibitors frequently used in the treatment of cancer include paclitaxel, docetaxel, vinblastine, vincristine, and vinorelbine.[4] Colchicine is a mitotic inhibitor used in the treatment of gout.[5]

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Use of mitotic inhibitors in cytogenetics

Cytogenetics, the study of chromosomal material by analysis of G-Banded chromosomes, uses mitotic inhibitors extensively. In order to prepare a slide for cytogenetic study, a mitotic inhibitor is added to the cells being studied. This stops the cells during mitosis, while the chromosomes are still visible. Once the cells are centrifuged and placed in a hypotonic solution, they swell, spreading the chromosomes. After preparation, the chromosomes of the cells can be viewed under a microscope to have the banding patterns of the chromosomes examined. This experiment is crucial to many forms of cancer research.

Specific agents

Taxanes

Taxanes are complex terpenes produced by the plants of the genus Taxus (yews). Originally derived from the Pacific yew tree, they are now synthesized artificially. Their principal mechanism is the disruption of the cell's microtubule function by stabilizing microtubule formation. Microtubules are essential to mitotic reproduction, so through the inactivation of the microtubule function of a cell, taxanes inhibit the cell's division.

Vinca alkaloids

Skeletal formula of vinblastine

Vinca alkaloids are amines produced by the hallucinogenic plant Catharanthus roseus (Madagascar Periwinkle). Vinca alkaloids inhibit microtubule depolymerization, thereby inhibiting mitosis.

Colchicine

Colchicine is an alkaloid derived from the autumn crocus (Colchicum autumnale). It inhibits mitosis by inhibiting microtubule polymerization. While colchicine is not used to treat cancer in humans, it is commonly used to treat acute attacks of gout.[5]

References

  1. ^ "What Are the Different Types of Chemotherapy Drugs?". American Cancer Society. http://www.cancer.org/docroot/ETO/content/ETO_1_4X_What_Are_The_Different_Types_Of_Chemotherapy_Drugs.asp. Retrieved 2007-08-05.  
  2. ^ "Definition of mitotic inhibitor". National Cancer Institute. http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46705. Retrieved 2007-08-05.  
  3. ^ "Treatment Options: Mitotic Inhibitors". Drug Digest. http://www.drugdigest.org/DD/HC/HCDrugClass/0,4055,47-8,00.html. Retrieved 2007-08-05.  
  4. ^ "What Are the Different Types of Chemotherapy Drugs?". American Cancer Society. http://www.cancer.org/docroot/ETO/content/ETO_1_4X_What_Are_The_Different_Types_Of_Chemotherapy_Drugs.asp. Retrieved 2007-08-05.  
  5. ^ a b Cyberbotanica. University of Texas. "Pharmacology of Colchicine." Last updated November 5, 1997. Last accessed July 14, 2007.
  6. ^ Saville M, Lietzau J, Pluda J, Feuerstein I, Odom J, Wilson W, Humphrey R, Feigal E, Steinberg S, Broder S (July 1 1995). "Treatment of HIV-associated Kaposi's sarcoma with paclitaxel.". Lancet 346 (8966): 26–8. doi:10.1016/S0140-6736(95)92654-2. PMID 7603142.  
  7. ^ Lyseng-Williamson KA, Fenton C. Docetaxel: a review of its use in metastatic breast cancer. Drugs 2005;65(17):2513-31.
  8. ^ Clarke SJ, Rivory LP. Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 1999;36(2):99-114
  9. ^ a b c d "Vincristine (Oncovin)". http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualdrugs/Vincristine. Retrieved 2007-08-05.  

See also


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