Related Experiment Video

Updated: Jul 11, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase

Jung-Hyun Park1, Hyun-Soon Jong, Sang Gyun Kim

  • 1National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Journal of Molecular Medicine (Berlin, Germany)
|September 14, 2007
PubMed

Insights

Histone deacetylase inhibitors (HDIs) selectively deplete Aurora-A kinase in cancer cells, causing mitotic defects and antitumor effects. This occurs via inhibition of HDAC6, leading to Aurora-A proteasomal degradation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The antitumor selectivity of histone deacetylase inhibitors (HDIs) is not fully understood.
  • Aurora-A kinase is crucial for mitosis and its dysregulation contributes to cancer.
  • HDIs have demonstrated significant antitumor potential.

Purpose of the Study:

  • To elucidate the molecular mechanism behind the tumor-selective action of HDIs.
  • To investigate the role of Aurora-A kinase in HDI-induced cancer cell death.
  • To identify specific HDIs effective against cancers with Aurora-A overexpression.

Main Methods:

  • Treatment of cancer and non-transformed cells with HDIs LAQ824 and SK-7068.
  • Analysis of mitotic spindle integrity and Aurora-A/B kinase levels.
  • Investigation of the interaction between HDAC6, Hsp90, and Aurora-A.

Main Results:

  • HDIs LAQ824 and SK-7068 induced selective mitotic defects in cancer cells.
  • Aurora-A was downregulated in HDI-treated cancer cells, but Aurora-B remained unaffected.
  • HDIs inhibited HDAC6, leading to Hsp90 acetylation, Aurora-A dissociation, and subsequent proteasomal degradation.

Conclusions:

  • HDIs achieve tumor selectivity by depleting Aurora-A kinase in cancer cells.
  • The mechanism involves HDAC6 inhibition, Hsp90 acetylation, and enhanced Aurora-A proteasomal degradation.
  • LAQ824 and SK-7068 show promise as cancer therapeutics, particularly for tumors overexpressing Aurora-A.

More Related Videos

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

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...