Related Experiment Video

Updated: Mar 30, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

8.8K

Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability

Hyun-Woo Kim1, Soo-A Kim2, Sang-Gun Ahn1

  • 1Department of Pathology, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.

Oncology Reports
|November 5, 2015
PubMed

Insights

Histone deacetylase (HDAC) inhibitors EX527 and AGK2 suppress cancer cell growth and migration. These compounds target Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2), impacting cell cycle and heat shock protein stability.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Histone deacetylases (HDACs), including Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2), are critical regulators of cellular processes like proliferation, differentiation, and apoptosis.
  • HDAC inhibitors represent a promising therapeutic strategy for various cancers.

Purpose of the Study:

  • To investigate the effects of Sirt1 and Sirt2 inhibitors, EX527 and AGK2, on cancer cell growth and migration.
  • To elucidate the molecular mechanisms underlying the anti-cancer effects of EX527 and AGK2.

Main Methods:

  • Cell viability assays and cell cycle analysis.
  • Soft agar colony formation assays.
  • Western blotting to assess protein expression and ubiquitination, including HSF1 and HSP27.
  • Scratch assays for cell migration analysis.

Main Results:

  • EX527 and AGK2 significantly suppressed cancer cell growth and induced G1 phase arrest by inhibiting Cyclin-dependent kinase 6 (Cdk6) and/or Cyclin-dependent kinase 4 (Cdk4) expression.
  • These inhibitors reduced colony formation in soft agar, indicating decreased anchorage-independent growth.
  • EX527 and AGK2 inhibited Heat Shock Factor 1 (HSF1) and Heat Shock Protein 27 (HSP27) expression and promoted HSF1 ubiquitination.
  • Sirt1 overexpression enhanced HSF1 expression and/or stabilization, promoting cell migration.

Conclusions:

  • EX527 and AGK2 exhibit anti-cancer properties by inhibiting cell proliferation and migration.
  • The observed effects are mediated through the modulation of cell cycle regulators (Cdk4/6) and the destabilization of HSF1 protein.
  • Targeting Sirt1 and Sirt2 with inhibitors like EX527 and AGK2 offers a potential therapeutic avenue for cancer treatment.

More Related Videos

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy09:17

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy

Published on: September 16, 2019

7.3K
Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

7.1K

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...
6.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.3K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.3K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
8.3K