Spindle poison

A spindle poison, also known as a spindle toxin, is a poison that disrupts cell division by affecting the protein threads that connect the centromere regions of chromosomes, known as spindles. Spindle poisons effectively cease the production of new cells by interrupting the mitosis phase of cell division at the spindle assembly checkpoint (SAC). However, as numerous and varied as they are, spindle poisons are not yet 100% effective at ending the formation of tumors (neoplasms).[1] Although not 100% effective, substantive therapeutic efficacy has been found in these types of chemotherapeutic treatments. The mitotic spindle is composed of microtubules (polymerized tubulin) that aid, along with regulatory proteins, each other in the activity of appropriately segregating replicated chromosomes. Certain compounds affecting the mitotic spindle have proven highly effective against solid tumors and hematological malignancies.

Two specific families of antimitotic agentsvinca alkaloids and taxanes — interrupt the cell’s division by the agitation of microtubule dynamics. The vinca alkaloids work by causing the inhibition of the polymerization of tubulin into microtubules, resulting in the G2/M arrest within the cell cycle and eventually cell death. In contrast, the taxanes arrest the mitotic cell cycle by stabilizing microtubules against depolymerization. Even though numerous other spindle proteins exist that could be the target of novel chemotherapeutics, tubulin-binding agents are the only types in clinical use. Agents that affect the motor protein kinesin are beginning to enter clinical trials.[2] Another type, paclitaxel, acts by attaching to tubulin within existing microtubules. Next, it stabilizes the polymer.

  1. ^ Wood KW, Cornwell WD, Jackson JR. (2001) Past and future of the mitotic spindle as an oncology target. Current Opinion in Pharmacology. 1:370–377. [PubMed]
  2. ^ Noelle S. Williams, Anthony W. G. Burgett, Ashley S. Atkins, Xiaodong Wang, Patrick G. Harran, and Steven L. McKnight. Proceedings of the National Academy of Sciences – U.S.A. 2007 February 13; 104(7): 2074–2079.

From Wikipedia, the free encyclopedia · View on Wikipedia

Developed by Tubidy