Abstract
Background and Aims: Polyphenolic acetates (PAs) have antioxidant/ pro-oxidant properties and can also acetylate proteins (enzymes) by a novel acetoxy drug: calreticulin transacetylase acetylation system. While PAs have been investigated as pharmacological agents for the treatment of various diseases, their potential as anti-cancer agents or their efficacy as an adjuvant in anti-cancer therapeutics remains to be explored. In the present study we investigated the cytotoxic and radio-sensitizing effects of 7, 8- diacetoxy-4-methyl coumarin (DAMC) and 7- acetoxy-4-methyl coumarin (7-AMC) in a human glioma cell line (BMG-1).
Methods: Cytotoxic and radio-sensitizing effects were investigated by studying reactive oxygen species (ROS) levels, metabolic viability, clonogenic survival, growth inhibition, cell cycle perturbation, DNA repair and cytogenetic damage, besides analyzing the histone (H3) acetylation.
Results: Exposure of cells to DAMC and 7-AMC for 24 h showed a dose dependent increase in toxicity as indicated by reduced metabolic viability, clonogenic survival and cell proliferation, with DAMC being more toxic than 7-AMC. The degree of radiosensitization by DAMC was also higher as compared to 7-AMC as reflected by a decrease in the clonogenicity, enhanced radiation-induced cell cycle perturbation and apoptosis. DAMC impaired the removal of radiation-induced DNA double stranded breaks (measured by γH2AX immuno- fluorescence) and enhanced the cytogenetic damage (micronuclei formation), leading to an increase in mitotic death. While DAMC alone induced pan nuclear γH2AX fluorescence, both pan nuclear and spatially restricted foci was observed with the combined treatment (DAMC + Radiation) suggesting a complex nature of DNA damage and repair. DAMC- induced cytotoxic and radio-sensitizing effects were independent of its pro-oxidant activity, whereas histone H3 lysine (9/14) hyperacetylation appeared to be a potential target, regulating cellular responses to ionizing radiation (IR).
Conclusions: The polyphenolic acetate 7, 8- diacetoxy-4-methyl coumarin (DAMC) demonstrates both anticancer effects and radiosensitizing potential under in vitro conditions.
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
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
The NLRP3 Inflammasome: An Attentive Arbiter of Inflammatory Response
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
The Role of Chromenes in Drug Discovery and Development
New Avenues in Drug Discovery and Bioactive Natural Products
Practice and Re-Emergence of Herbal Medicine
22
