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Updated: Oct 10, 2025

Live Cell Imaging of Chromosome Segregation During Mitosis
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Live Cell Imaging of Chromosome Segregation During Mitosis

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TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic

Girish Rajendraprasad1, Susana Eibes1, Claudia Guasch Boldú1

  • 1Cell Division and Cytoskeleton, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Cancers
|December 10, 2021
PubMed

Insights

TH588, a microtubule-targeting agent, stabilizes mitotic spindles, causing cell division errors and death. This mechanism mirrors low-dose nocodazole, impacting cancer treatment strategies.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Microtubule-targeting agents (MTAs) are vital in cancer therapy by disrupting microtubule dynamics.
  • TH588 exhibits anticancer properties, partly due to its MTH1-inhibiting and microtubule-targeting abilities.
  • The precise impact of TH588 on mitotic spindle microtubule dynamics was previously uncharacterized.

Purpose of the Study:

  • To investigate the effects of TH588 on spindle-associated microtubules during cell division.
  • To compare TH588's mechanism with that of low-dose nocodazole on microtubule dynamics.
  • To elucidate the consequences of TH588-induced microtubule stabilization on chromosome congression and cell fate.

Main Methods:

  • In-depth analysis of TH588's impact on mitotic spindle microtubules.
  • Comparative study using low-dose nocodazole as a reference MTA.
  • Microscopy and cell cycle analysis to assess microtubule dynamics, chromosome attachment, and cell division outcomes.

Main Results:

  • Both TH588 and low-dose nocodazole significantly reduce microtubule turnover within the mitotic spindle.
  • This stabilization results in premature kinetochore-microtubule end-on attachments on uncongressed chromosomes.
  • Delayed cell division and subsequent cell death or aberrant division with uncongressed chromosomes were observed.

Conclusions:

  • TH588 acts as an MTA by stabilizing mitotic spindle microtubules, similar to nocodazole.
  • The observed microtubule stabilization disrupts chromosome alignment, leading to cell cycle arrest and potential cell death.
  • These findings highlight TH588's potential as a cancer therapeutic agent through its unique mechanism of action on the mitotic spindle.
Keywords:
cancer therapycell divisionmicrotubule dynamicsmicrotubule-targeting agentsmitotic spindle

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