Inhibition of PCAF by Anacardic Acid Derivative Leads to Apoptosis and Breaks Resistance to DNA Damage in BCR-ABL-expressing Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

Download PDF Flyer

Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

Inhibition of PCAF by Anacardic Acid Derivative Leads to Apoptosis and Breaks Resistance to DNA Damage in BCR-ABL-expressing Cells

Anti-Cancer Agents in Medicinal Chemistry, 13(5): 762-767.

Author(s): Monika Kusio- Kobialka, Wioleta Dudka- Ruszkowska, Massimo Ghizzoni, Frank J. Dekker and Katarzyna Piwocka.

Affiliation: Nencki Institute of Experimental Biology; 3, Pasteur, Str, 02-093 Warsaw, Poland.


Acetylation of histones and nonhistone proteins is a posttranslational modification which plays a major role in the regulation of intracellular processes involved in tumorigenesis. It was shown that different acetylation of proteins correlates with development of leukemia. It is proposed that histone acetyltransferases (HATs) are important novel drug targets for leukemia treatment, however data are still not consistent. Our previous data showed that a derivative of anacardic acid - small molecule MG153, which has been designed and synthesized to optimize the HAT inhibitory potency of anacardic acid, is a potent inhibitor of p300/CBP associated factor (PCAF) acetyltransferase. Here we ask whether inhibition of PCAF acetyltransferase with MG153 will show proapoptotic effects in cells expressing BCR-ABL, which show increased PCAF expression and are resistant to apoptosis. We found that inhibition of PCAF decreases proliferation and induces apoptosis, which correlates with loss of the mitochondrial membrane potential and DNA fragmentation. Importantly, cells expressing BCR-ABL are more sensitive to PCAF inhibition compared to parental cells without BCRABL. Moreover, inhibition of PCAF in BCR-ABL-expressing cells breaks their resistance to DNA damage-induced cell death. These findings provide direct evidence that targeting the PCAF alone or in combination with DNA-damaging drugs shows cytotoxic effects and should be considered as a prospective therapeutic strategy in chronic myeloid leukemia cells. Moreover, we propose that anacardic acid derivative MG153 is a valuable agent and further studies validating its therapeutic relevance should be performed.


Acetylation, anacardic acid, apoptosis, BCR-ABL, p300/CBP associated factor (PCAF).

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 13
Issue Number: 5
First Page: 762
Last Page: 767
Page Count: 6
DOI: 10.2174/1871520611313050010
Price: $58

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science