Abstract
Bisacylimidoselenocarbamate derivatives (BSC) are potent anticancer agents with a strong cytotoxic activity against different types of tumour cells. Based in phosphatidylserine exposure on the cell membranes we show that BSC treatment resulted in enhanced cell death in leukaemia CCRF-CEM cells. DNA fragmentation detection in breast adenocarcinoma MCF-7 cells showed that BSC triggered cell death is concentration and time dependent. We also show that two of these compounds, BSC 3g and 3n, cause cell-cycle arrest in the late G2/M in MCF-7 cells. Consistent with this, a reduction in CDK1 and CDK2 expression with no change in cyclin A an B1 was observed in this cell line. Activation of caspase-2 was also detected. However, the involvement of the caspase-dependent pathway in the process of cell death induced by either BSC 3g or 3n is discarded since cell death could not be prevented by pretreatment with the pancaspase inhibitor z-VAD-fmk. Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF-7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis.
Keywords: Bisacylimidoselenocarbamates, CDK1, Chk2, G2/M cell cycle arrest, MCF-7 breast cancer cells
Current Medicinal Chemistry
Title:Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells
Volume: 20 Issue: 12
Author(s): Iranzu Lamberto, Daniel Plano, Esther Moreno, Maria Font, Juan Antonio Palop, Carmen Sanmartin and Ignacio Encio
Affiliation:
Keywords: Bisacylimidoselenocarbamates, CDK1, Chk2, G2/M cell cycle arrest, MCF-7 breast cancer cells
Abstract: Bisacylimidoselenocarbamate derivatives (BSC) are potent anticancer agents with a strong cytotoxic activity against different types of tumour cells. Based in phosphatidylserine exposure on the cell membranes we show that BSC treatment resulted in enhanced cell death in leukaemia CCRF-CEM cells. DNA fragmentation detection in breast adenocarcinoma MCF-7 cells showed that BSC triggered cell death is concentration and time dependent. We also show that two of these compounds, BSC 3g and 3n, cause cell-cycle arrest in the late G2/M in MCF-7 cells. Consistent with this, a reduction in CDK1 and CDK2 expression with no change in cyclin A an B1 was observed in this cell line. Activation of caspase-2 was also detected. However, the involvement of the caspase-dependent pathway in the process of cell death induced by either BSC 3g or 3n is discarded since cell death could not be prevented by pretreatment with the pancaspase inhibitor z-VAD-fmk. Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF-7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis.
Export Options
About this article
Cite this article as:
Lamberto Iranzu, Plano Daniel, Moreno Esther, Font Maria, Antonio Palop Juan, Sanmartin Carmen and Encio Ignacio, Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells, Current Medicinal Chemistry 2013; 20 (12) . https://dx.doi.org/10.2174/0929867311320120010
DOI https://dx.doi.org/10.2174/0929867311320120010 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
- 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
-
State of the Art and Perspectives in Food Allergy (Part I): Diagnosis
Current Pharmaceutical Design New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer
Current Pharmaceutical Design Biotechnological Production of Taxol and Related Taxoids: Current State and Prospects
Anti-Cancer Agents in Medicinal Chemistry n-3 Polyunsaturated Fatty Acids and the Prevention of Colorectal Cancer: Molecular Mechanisms Involved
Current Medicinal Chemistry Herpes Simplex Virus Vectors for the Nervous System
Current Gene Therapy Chemoresistance in High-Grade Gliomas: Relevance of Adenosine Signalling in Stem-Like Cells of Glioblastoma Multiforme
Current Drug Targets The Link Between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy
Drug Metabolism Letters Role of Hsp70 in Cancer Growth and Survival
Protein & Peptide Letters Drug Targets in Human T-Lymphotropic Virus Type 1 (HTLV-1) Infection
Infectious Disorders - Drug Targets MicroRNAs in Cancer: Small Molecules, Big Chances
Anti-Cancer Agents in Medicinal Chemistry Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs
Current Medicinal Chemistry The Influence of Traumatic Lumbar Puncture (TLP) on Outcome of Pediatric Patients
Current Pediatric Reviews Herpesvirus Saimiri-Based Gene Delivery Vectors
Current Gene Therapy Developments of Combretastatin A-4 Derivatives as Anticancer Agents
Current Medicinal Chemistry Nitric Oxide: Cancer Target or Anticancer Agent?
Current Cancer Drug Targets Anticancer α-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes
Current Protein & Peptide Science The Emerging Role of Bcr-Abl-Induced Cystoskeletal Remodeling in Systemic Persistence of Leukemic Stem Cells
Current Drug Delivery A Comparison of Physicochemical Property Profiles of Marketed Oral Drugs and Orally Bioavailable Anti-Cancer Protein Kinase Inhibitors in Clinical Development
Current Topics in Medicinal Chemistry Self-immolative Linkers in Prodrugs and Antibody Drug Conjugates in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery A Review of the Primer Approximation Multiplex PCR (PAMP) Technique for Detecting Large Scale Cancer Genomic Lesions
Current Bioinformatics