Abstract
Epigenetic changes including DNA methylation, histone modifications, chromatin remodeling and microRNAs play critical roles in tumorigenesis and tumor development. Reversal of epigenetic changes sensitizes some tumor cells to radiation.
DNMT-I enhances the response of tumor cells to radiotherapy. AZA demethylated promoters of genes related to ionizing radiation response, such as p16 and hMLH1. The genes expression of the p53, RASSF1, and DAPK gene families was increased by 5-aza-CdR, which induces G2-M phase arrest and increased apoptosis.
HDAC-I has both anti-tumor activity and radiation sensitization activity. HDAC-I disrupts both DNA damage sensing and repair processes: HDAC-I disrupts the association between HDAC enzyme and DNA sensor proteins 53BP1 and ATM. HDAC-I changes the acetylation status of both proteins involved in homologous recombination (HR) repair pathway which include BRCA1, Rad51, and Rad50, and proteins involved in non-homologous end joining (NHEJ) repair pathway which include Ku70, and DNA-PK. HDACs are also implicated as essential components in the DNA repair process itself. Besides the radiosensitizing mechanism of intervention of DNA repair, other possible mechanisms including cell cycle redistribution, acetylation of Hsp90, increased apoptosis, and decreased survival signals are also suggested.
Some miRNAs also regulate the radiosensitivity of tumor cells. Inhibition of miR-34 expression or function, downregulation of miR-155, upregulation of miR-18a, Overexpression let-7g or knocking down LIN28B, and ectopically overexpressed miR-10 in cells with low endogenous miR-101 level increase the response of cells to irradiation. For radiation-resistant cancer cells, miR-7 sensitizes the radiation for cells which activated EGFR-PI3K-AKT signaling pathway;
Keywords: Demethylating agents, histone deacetylase inhibitors, anticancer drugs, radiotherapy, radiosensitization, epigenetic.
Current Pharmaceutical Design
Title:Epigenetic Interventions Increase the Radiation Sensitivity of Cancer Cells
Volume: 20 Issue: 11
Author(s): Juan Ren, Yongli Chu, Hongbing Ma, Yuelang Zhang, Xiaozhi Zhang, Dongli Zhao, Zongfang Li, Jiansheng Wang, Yan-e Gao, Lisha Xiao, Rui Liu, Jiansheng Qian, Yan Liu, Hongxia Wei and Shiwen Jiang
Affiliation:
Keywords: Demethylating agents, histone deacetylase inhibitors, anticancer drugs, radiotherapy, radiosensitization, epigenetic.
Abstract: Epigenetic changes including DNA methylation, histone modifications, chromatin remodeling and microRNAs play critical roles in tumorigenesis and tumor development. Reversal of epigenetic changes sensitizes some tumor cells to radiation.
DNMT-I enhances the response of tumor cells to radiotherapy. AZA demethylated promoters of genes related to ionizing radiation response, such as p16 and hMLH1. The genes expression of the p53, RASSF1, and DAPK gene families was increased by 5-aza-CdR, which induces G2-M phase arrest and increased apoptosis.
HDAC-I has both anti-tumor activity and radiation sensitization activity. HDAC-I disrupts both DNA damage sensing and repair processes: HDAC-I disrupts the association between HDAC enzyme and DNA sensor proteins 53BP1 and ATM. HDAC-I changes the acetylation status of both proteins involved in homologous recombination (HR) repair pathway which include BRCA1, Rad51, and Rad50, and proteins involved in non-homologous end joining (NHEJ) repair pathway which include Ku70, and DNA-PK. HDACs are also implicated as essential components in the DNA repair process itself. Besides the radiosensitizing mechanism of intervention of DNA repair, other possible mechanisms including cell cycle redistribution, acetylation of Hsp90, increased apoptosis, and decreased survival signals are also suggested.
Some miRNAs also regulate the radiosensitivity of tumor cells. Inhibition of miR-34 expression or function, downregulation of miR-155, upregulation of miR-18a, Overexpression let-7g or knocking down LIN28B, and ectopically overexpressed miR-10 in cells with low endogenous miR-101 level increase the response of cells to irradiation. For radiation-resistant cancer cells, miR-7 sensitizes the radiation for cells which activated EGFR-PI3K-AKT signaling pathway;
Export Options
About this article
Cite this article as:
Ren Juan, Chu Yongli, Ma Hongbing, Zhang Yuelang, Zhang Xiaozhi, Zhao Dongli, Li Zongfang, Wang Jiansheng, Gao Yan-e, Xiao Lisha, Liu Rui, Qian Jiansheng, Liu Yan, Wei Hongxia and Jiang Shiwen, Epigenetic Interventions Increase the Radiation Sensitivity of Cancer Cells, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990529
DOI https://dx.doi.org/10.2174/13816128113199990529 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Regulation of Apoptosis and Cell Survival by Resveratrol
Mini-Reviews in Organic Chemistry Role of Inflammatory Mediators in Angiogenesis
Current Drug Targets - Inflammation & Allergy Biological Effects, Total Phenolic Content and Flavonoid Concentrations of Fragrant Yellow Onion (Allium flavum L.)
Medicinal Chemistry Clinical Pharmacology of Serotonin Receptor Type 3 (5-HT3) Antagonists
Current Medicinal Chemistry - Central Nervous System Agents New Antitumour Natural Products from Marine Red Algae: Covering the Period from 2003 to 2012
Mini-Reviews in Medicinal Chemistry Prodrugs in Genetic Chemoradiotherapy
Current Pharmaceutical Design Cutting the Limits of Aminobisphosphonates: New Strategies for the Potentiation of their Anti-Tumour Effects
Current Cancer Drug Targets Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing
Current Medicinal Chemistry New Use for Old Drugs? Prospective Targets of Chloroquines in Cancer Therapy
Current Drug Targets Genetic Variations in Telomere Maintenance, with Implications on Tissue Renewal Capacity and Chronic Disease Pathologies
Current Pharmacogenomics and Personalized Medicine Cell Surface Nucleolin as a Target for Anti-Cancer Therapies
Recent Patents on Anti-Cancer Drug Discovery The Endocannabinoid System in the Cancer Therapy: An Overview
Current Medicinal Chemistry Role of NF-κB and NF-κB-regulated Gene Products in Chemoresistance and Radioresistance
Current Cancer Therapy Reviews Biotransformations of Prenylated Hop Flavonoids for Drug Discovery and Production
Current Drug Metabolism Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology Dietary Agents for Prostate Cancer Chemoprevention: An Overview
Current Cancer Therapy Reviews Colchicine: An Ancient Drug with Multiple Benefits
Current Pharmaceutical Design Synthesis of pyridyl benzimidazoles encompassing 4-thiazolidinone derivatives as potential antimicrobial agents
Letters in Drug Design & Discovery Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance
Anti-Cancer Agents in Medicinal Chemistry