Abstract
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.
Keywords: Acetylation, anacardic acid, apoptosis, BCR-ABL, p300/CBP associated factor (PCAF).
Anti-Cancer Agents in Medicinal Chemistry
Title:Inhibition of PCAF by Anacardic Acid Derivative Leads to Apoptosis and Breaks Resistance to DNA Damage in BCR-ABL-expressing Cells
Volume: 13 Issue: 5
Author(s): Monika Kusio- Kobialka, Wioleta Dudka- Ruszkowska, Massimo Ghizzoni, Frank J. Dekker and Katarzyna Piwocka
Affiliation:
Keywords: Acetylation, anacardic acid, apoptosis, BCR-ABL, p300/CBP associated factor (PCAF).
Abstract: 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.
Export Options
About this article
Cite this article as:
Kobialka Monika Kusio-, Ruszkowska Wioleta Dudka-, Ghizzoni Massimo, Dekker Frank J. and Piwocka Katarzyna, 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 2013; 13 (5) . https://dx.doi.org/10.2174/1871520611313050010
DOI https://dx.doi.org/10.2174/1871520611313050010 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Multidetector Computed Tomography of Iatrogenic Urinary Trauma - Pictorial Review
Current Medical Imaging Regulation of Bcl-2 Family Proteins by Posttranslational Modifications
Current Molecular Medicine Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry Patent Selections:
Current Biomarkers (Discontinued) The Genetic Basis of New Treatment Modalities in Melanoma
Current Drug Targets Prokaryotic Arsenate Reductase Enhances Arsenate Resistance in Mammalian Cells
Recent Patents on Food, Nutrition & Agriculture Photothermal Ablation of Cancer Cells Using Folate-Coated Gold/ Graphene Oxide Composite
Current Drug Delivery Tumor Invasion and Oxidative Stress: Biomarkers and Therapeutic Strategies
Current Molecular Medicine Amygdalin from Apricot Kernels Induces Apoptosis and Causes Cell Cycle Arrest in Cancer Cells: An Updated Review
Anti-Cancer Agents in Medicinal Chemistry Dehydroleucodine Induces a TP73-dependent Transcriptional Regulation of Multiple Cell Death Target Genes in Human Glioblastoma Cells
Anti-Cancer Agents in Medicinal Chemistry D Allele Frequency in Insertion/Deletion Polymorphism of the Angiotensin Converting Enzyme (ACE) Gene is Associated with Development of Breast Cancer Risk in Indian Women
Current Proteomics Discovery of New Inhibitors of Urease Enzyme: A Study Using STD-NMR Spectroscopy
Letters in Drug Design & Discovery Potential Anti-cancer Drugs Commonly Used for Other Indications
Current Cancer Drug Targets A Comprehensive Study of Pharmacological Behaviors, Nano-Formulations, and Applications of Rosemary
The Natural Products Journal SELDI Protein Chip Technology for the Detection of Serum Biomarkers for Liver Disease
Protein & Peptide Letters Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions
Current Drug Metabolism Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry HGF/MET Signaling in Ovarian Cancer
Current Molecular Medicine Dendritic Cells and their Receptors in Antitumor Immune Response
Current Molecular Medicine