Tubulin Inhibitor
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A mitotic inhibitor is a drug that inhibits
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body ( metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics (the study of chromosomes), where they stop cell division at a stage where chromosomes can be easily examined. Mitotic inhibitors are derived from natural substances such as plant
alkaloids Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar st ...
, and prevent cells from undergoing mitosis by disrupting microtubule polymerization, thus preventing cancerous growth. Microtubules are long, ropelike proteins that extend through the cell and move cellular components around. Microtubules are long polymers made of smaller units ( monomers) of the protein tubulin. Microtubules are created during normal cell functions by assembling (polymerizing) tubulin components, and are disassembled when they are no longer needed. One of the important functions of microtubules is to move and separate chromosomes and other components of the cell for cell division (
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
). Mitotic inhibitors interfere with the assembly and disassembly of tubulin into microtubule polymers. This interrupts cell division, usually during the mitosis (M) phase of the cell cycle when two sets of fully formed chromosomes are supposed to separate into daughter cells. Examples of mitotic inhibitors frequently used in the treatment of cancer include paclitaxel, docetaxel, vinblastine, vincristine, and vinorelbine. Colchicine and griseofulvin are mitotic inhibitors used in the treatment of gout and
toenail fungus Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, ...
, respectively.


Use 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 In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane-i ...
, 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 Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
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. * Paclitaxel—used to treat lung cancer, ovarian cancer, breast cancer, and advanced forms of Kaposi's sarcoma. * Docetaxel—used to treat breast, ovarian, and non-small cell lung cancer.


Vinca alkaloids

Vinca alkaloids are amines produced by the
hallucinogenic plant Psychoactive plants are plants, or preparations thereof, that upon ingestion induce psychotropic effects. As stated in a reference work: Psychoactivity may include sedative, stimulant, euphoric, deliriant, and hallucinogenic effects. Several ...
'' Catharanthus roseus'' (Madagascar Periwinkle). Vinca alkaloids inhibit
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
polymerization. * Vinblastine—used to treat leukaemia, Hodgkin's lymphoma, non-small cell lung cancer, breast cancer and testicular cancer. It is also a component in a large number of chemotherapy regimens. * Vincristine—used to treat lymphoma, breast cancer, lung cancer, and
acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
. * Vindesine—used to treat leukaemia, lymphoma,
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
, breast cancer, and lung cancer. * Vinorelbine—used to treat breast cancer and non-small-cell lung cancer.


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.


Podophyllotoxin

Podophyllotoxin derived from the
may apple ''Podophyllum'' is a genus of flowering plant in the family Berberidaceae, native from Afghanistan to China, and from southeast Canada to the central and eastern United States. The genus was first described by Carl Linnaeus in 1753. Taxonomy Th ...
plant, is used to treat viral skin infections and synthetic analogues of the molecule are used to treat certain types of cancer.


Griseofulvin

Griseofulvin, derived from a species of '' Penicillium'' is an mitotic inhibitor that is used as an antifungal drug. It inhibits the assembly of fungal microtubules


Others

Glaziovianin A is typically isolated from the leaves of the Brazilian tree ''
Ateleia glazioviana ''Ateleia'' is a genus of legume in the family Fabaceae. It contains the following species: * '' Ateleia albolutescens'' Mohlenbr. * ''Ateleia apetala'' Griseb. * ''Ateleia arsenii'' Standl. * ''Ateleia glazioveana'' Baill. * ''Ateleia gummifer ...
'' Baill.Fighting Cancer with a Pinch of Parsley and Dill.
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See also

* Cytogenetics * Discovery and development of tubulin inhibitors * Medicinal molds *
Mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...


References

{{DEFAULTSORT:Mitotic Inhibitor Mitosis