Abstract
The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.
Keywords: Apoptosis, caspase, human breast cancer adenoma, mitochondria, MCF-7 cell line, MMD, quinazolinone.
Current Pharmaceutical Design
Title:Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
Volume: 21 Issue: 23
Author(s): Maryam Zahedifard, Fadhil Lafta Faraj, Mohammadjavad Paydar, Chung Yeng Looi, Pouya Hasandarvish, Maryam Hajrezaie, Behnam Kamalidehghan, Nazia Abdul Majid, Shaden A.M. Khalifa, Hapipah Mohd Ali, Mahmood Ameen Abdulla and Hesham R. El-Seedi
Affiliation:
Keywords: Apoptosis, caspase, human breast cancer adenoma, mitochondria, MCF-7 cell line, MMD, quinazolinone.
Abstract: The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.
Export Options
About this article
Cite this article as:
Zahedifard Maryam, Faraj Lafta Fadhil, Paydar Mohammadjavad, Looi Yeng Chung, Hasandarvish Pouya, Hajrezaie Maryam, Kamalidehghan Behnam, Majid Abdul Nazia, Khalifa A.M. Shaden, Ali Mohd Hapipah, Abdulla Ameen Mahmood and El-Seedi R. Hesham, Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells, Current Pharmaceutical Design 2015; 21 (23) . https://dx.doi.org/10.2174/1381612821666150326104952
DOI https://dx.doi.org/10.2174/1381612821666150326104952 |
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
-
Targeting the Nogo-A Signalling Pathway to Promote Recovery Following Acute CNS Injury
Current Pharmaceutical Design Targeting Platinum Resistant Disease in Ovarian Cancer
Current Medicinal Chemistry Dysfunctions of the Diffusional Membrane Pathways Mediated Hemichannels in Inherited and Acquired Human Diseases
Current Vascular Pharmacology Poly (ADP-Ribosyl) Polymerase 1 Inhibitors: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery Anti-Inflammatory and Anti-Neoplastic Actions of Resveratrol
Current Nutrition & Food Science Obesity: An Emerging Importance of Progenitors
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Tyrosine Kinase Mutations in Human Cancer
Current Molecular Medicine Naringenin and Ellagic Acid Reduce Tetrazolium Salt in the Absence of Cells
The Natural Products Journal Eliminating Ovarian Cancer Stem Cells: A Potential Therapeutic Target for Ovarian Cancer Chemoresistance
Current Protein & Peptide Science Alpha-Emitters for Immuno-Therapy: A Review of Recent Developments from Chemistry to Clinics
Current Topics in Medicinal Chemistry Latest Results for Anti-Angiogenic Drugs in Cancer Treatment
Current Pharmaceutical Design Targeting the p53-Family in Cancer and Chemosensitivity: Triple Threat
Current Drug Targets Effect of Free and in Poly(η-caprolactone) Nanoparticles Incorporated New Type 1 17β -Hydroxysteroid Dehydrogenase Inhibitors on Cancer Cells
Current Nanoscience Pharmacological Approaches to Chronic Spinal Cord Injury
Current Pharmaceutical Design Blood-Brain Barrier ABC-transporter P-glycoprotein in Alzheimer's Disease: Still a Suspect?
Current Pharmaceutical Design Rational Targeting of Peroxisome Proliferating Activated Receptor Subtypes
Current Medicinal Chemistry Clinical Pharmacology of Trastuzumab
Current Clinical Pharmacology Genetic Analysis of CYP2D6 Polymorphism in Indian Populations and its Pharmacogenetic Implications
Current Pharmacogenomics and Personalized Medicine Structure-Bioactivity Relationship Study of Xanthene Derivatives: A Brief Review
Current Organic Synthesis Extrahepatic Targets and Cellular Reactivity of Drug Metabolites
Current Medicinal Chemistry