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 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 ...

, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

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 A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...

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 (

). 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 The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

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 Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...

, docetaxel, vinblastine,

vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

, and

vinorelbine Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mou ...

. Colchicine and

griseofulvin Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth. C ...

are mitotic inhibitors used in the treatment of

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...

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 A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

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

terpene Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ar ...

s produced by the plants of the genus ''

Taxus ''Taxus'' is a genus of coniferous trees or shrubs known as yews in the family Taxaceae. They are relatively slow-growing and can be very long-lived, and reach heights of , with trunk girth averaging . They have reddish bark, lanceolate, flat, ...

'' (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 Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...

—used to treat

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

, and advanced forms of

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

. * Docetaxel—used to treat breast, ovarian, and non-small cell lung cancer.

Vinca alkaloids

Vinca alkaloids are

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

s 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

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer, monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are ...

. * Vinblastine—used to treat

leukaemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

, Hodgkin's lymphoma, non-small cell lung cancer, breast cancer and

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an u ...

. It is also a component in a large number of chemotherapy regimens. *

Vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

—used to treat

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

, 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 Vindesine, also termed Eldisine, is a semisynthetic vinca alkaloid derived from the flowering plant ''Catharanthus roseus.'' Like the natural (e.g. vinblastine and vincristine) and semisynthetic vinca alkaloids (e.g. vinorelbine and vinflunine) ...

—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 Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mou ...

—used to treat breast cancer and non-small-cell lung cancer.

Colchicine

Colchicine is an

alkaloid 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 ...

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

Podophyllotoxin

Podophyllotoxin Podophyllotoxin (PPT) is the active ingredient in Podofilox, which is a medical cream that is used to treat genital warts and molluscum contagiosum. It is not recommended in HPV infections without external warts. It can be applied either by a he ...

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 Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth. C ...

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

fungal A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...

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.
/ref>

References

{{DEFAULTSORT:Mitotic Inhibitor Mitosis