Related Experiment Video

Updated: Jun 25, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

Short and long-term tumor cell responses to Aurora kinase inhibitors

Megan R Dreier1, Aaron Z Grabovich, Jamie D Katusin

  • 1Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA. megan.dreier@utoledo.edu

Experimental Cell Research
|February 24, 2009
PubMed

Insights

p53 is crucial for cell cycle arrest when Aurora kinases are inhibited. However, this p53-dependent block is not immediate or absolute, and cells can evade Aurora kinase inhibitors through novel mechanisms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Aurora kinases play a critical role in mitosis.
  • Aurora kinase inhibitors are investigated as cancer therapeutics.
  • p53 tumor suppressor function is vital in cell cycle regulation.

Purpose of the Study:

  • To kinetically analyze the effects of Aurora kinase inhibitors (ZM447439 and VE-465) on cell lines with differing p53 function.
  • To investigate the role of p53 in mediating cell cycle arrest induced by Aurora kinase inhibition.
  • To explore mechanisms by which cells evade killing by Aurora kinase inhibitors.

Main Methods:

  • Kinetic analysis of isogenic cell lines with varying p53 status.
  • Treatment with Aurora kinase inhibitors ZM447439 and VE-465.
  • Assessment of cell cycle arrest, DNA damage (gammaH2A.X accumulation), and long-term cell survival.

Main Results:

  • p53 is required for efficient cell cycle arrest upon Aurora kinase inhibition.
  • The p53-mediated cell cycle block is neither immediate nor absolute.
  • ZM447439 induces DNA damage, leading to p53 induction.
  • Cells can evade long-term killing by ZM447439 via non-classical drug-resistance mechanisms.

Conclusions:

  • p53 status significantly influences the response to Aurora kinase inhibitors.
  • Aurora kinase inhibitors can induce DNA damage and p53-dependent cell cycle arrest.
  • Novel mechanisms of resistance or evasion exist for Aurora kinase inhibitors, warranting further investigation for effective cancer therapy.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...