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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). Unfortunately, spindle poisons, as numerous and varied as they are, still are yet to be 100% effective at ending the formation of tumors (neoplasms).〔Wood KW, Cornwell WD, Jackson JR. (2001) Past and future of the mitotic spindle as an oncology target. Curr Opin Pharmacol 1:370–377. ()〕
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 agents, vinca 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 proteinkinesin are beginning to enter clinical trials.〔Noelle S. Williams, Anthony W. G. Burgett, Ashley S. Atkins, Xiaodong Wang, Patrick G. Harran, and Steven L. McKnight. Proc Natl Acad Sci U S A. 2007 February 13; 104(7): 2074–2079.〕 Another type, Paclitaxel, acts by attaching to tubulin within existing microtubules. Next, it stabilizes the polymer.
==Spindle assembly checkpoint (SAC)==
Normally, cells duplicate their genetic material and then produce two equal daughter cells. Tampering with this tightly monitored distribution system can result in the production of irregular chromosome content, within each cell, commonly referred to as aneuploidy. It is no surprise that cells have developed various checkpoints to carry out mitosis with great accuracy. Early research led scientists to discover that spindle poisons, which were inserted to cells, caused a considerable reduction in the number of cells that exited mitosis, yet the number of cells that entered mitosis dramatically increased. The SAC was found to be the key signaling pathway to the mitotic arrest. The precise division of chromosomes is the primary responsibility of SAC. Its origin stems from kinetochores, proteins that aid in joining DNA and microtubules on the chromatids. Only one unattached kinetochore is required to fuel a response that ultimately blocks cell cycle progression. The end result is each chromosome is attached to the spindle in the initial stage of anaphase.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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