Colcemid

Used in cytogenetics, colcemid, also known as demecolcine, is related to colchicine but it is less toxic. It depolymerises microtubules and limits microtubule formation (inactivates spindle fibre formation), thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.

Mechanism of Action

Colcemid is a microtubule-depolymerizing drug like vinblastine. It acts by two distinct mechanisms. At very low concentration it binds to microtubule plus end to suppress microtubule dynamics.[1] Recent study has found at higher concentration colcemid can promote microtubule detachment from microtubule organizing center. Detached microtubules with unprotected minus ends depolymerize with time. Cytotoxicity of the cells seems to correlate better with microtubule detachment.[2] Lower concentrations affect microtubule dynamics and cell migration.[2]

Uses

Colcemid is used primarily for scientific research in cells. It is used in a variety of ways, however, until recently, was used mostly for the study of mitosis in cells. For example, microtubules are necessary for the splitting of cells. More importantly, the movement of chromosomes during the M phase. Colcemid inhibition of microtubules causes aneuploidy in mitotic cells where the microtubules fall apart or are suppressed before they can complete their function of pulling chromosomes into the daughter cell, also known as nondisjunction of chromosomes.[3] Colcemid, depending on dosage, has also been found to cause DNA fragmentation of chromosomes in micronuclei when nondisjunction occurs.[4]

References

  1. ↑ Jordan, Mary Ann; Wilson, Leslie (2004). "Microtubules as a target for anticancer drugs". Nature reviews. Cancer 4 (4): 253–65. doi:10.1038/nrc1317. PMID 15057285.
  2. 1 2 Yang, Hailing; Ganguly, Anutosh; Cabral, Fernando (2010). "Inhibition of Cell Migration and Cell Division Correlates with Distinct Effects of Microtubule Inhibiting Drugs". The Journal of Biological Chemistry 285 (42): 32242–50. doi:10.1074/jbc.M110.160820. PMC 2952225. PMID 20696757.
  3. ↑ Hashimoto, Kiyohiro; Todo, Takeshi (2013-07-01). "Mitotic slippage underlies the relationship between p53 dysfunction and the induction of large micronuclei by colcemid". Mutagenesis 28 (4): 457–464. doi:10.1093/mutage/get021. ISSN 0267-8357. PMID 23702691.
  4. ↑ Yamamoto, Mika; Wakata, Akihiro; Aoki, Yoshinobu; Miyamae, Yoichi; Kodama, Seiji (2014-04-01). "Chromosome loss caused by DNA fragmentation induced in main nuclei and micronuclei of human lymphoblastoid cells treated with colcemid". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 762: 10–16. doi:10.1016/j.mrfmmm.2014.02.002.
This article is issued from Wikipedia - version of the Wednesday, November 25, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.