Abstract
In cancer chemotherapy, it is necessary to design an agent that suppresses or inhibits the targets that influence cell growth and apoptosis. We focus on the apoptotic pathway via mitochondria in this article. In this pathway, c-Jun N-terminal kinase (JNK), one of the stress activated protein kinases, is predominantly activated by apoptotic stimuli. JNK activity is inhibited by the binding of glutathione S-transferase P1-1 (GST P1-1) through protein-protein interactions. It has been noted that GST P1-1 overexpression plays an important role in carcinogenesis and in part in the MDR phenotype. We show several useful modifications of an anticancer agent that suppress the enzyme activity and expression of GST P1-1. The release of cytochrome c from mitochondria to the cytosol during apoptosis is mediated by the mitochondrial permeability transition pore, which is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti- apoptotic Bax-Bcl-2 protein family, cyclophilin D, and adenine nucleotide (ADP / ATP) translocators. We propose some drugs, including a proteasome inhibitor that can triger the permeability transition.
Keywords: Chemotherapeutic, proteasome, adenine nucleotide, cyclophilin D
Current Cancer Drug Targets
Title: Chemotherapeutic Agents That Induce Mitochondrial Apoptosis
Volume: 4 Issue: 7
Author(s): Tadashi Asakura and Kiyoshi Ohkawa
Affiliation:
Keywords: Chemotherapeutic, proteasome, adenine nucleotide, cyclophilin D
Abstract: In cancer chemotherapy, it is necessary to design an agent that suppresses or inhibits the targets that influence cell growth and apoptosis. We focus on the apoptotic pathway via mitochondria in this article. In this pathway, c-Jun N-terminal kinase (JNK), one of the stress activated protein kinases, is predominantly activated by apoptotic stimuli. JNK activity is inhibited by the binding of glutathione S-transferase P1-1 (GST P1-1) through protein-protein interactions. It has been noted that GST P1-1 overexpression plays an important role in carcinogenesis and in part in the MDR phenotype. We show several useful modifications of an anticancer agent that suppress the enzyme activity and expression of GST P1-1. The release of cytochrome c from mitochondria to the cytosol during apoptosis is mediated by the mitochondrial permeability transition pore, which is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti- apoptotic Bax-Bcl-2 protein family, cyclophilin D, and adenine nucleotide (ADP / ATP) translocators. We propose some drugs, including a proteasome inhibitor that can triger the permeability transition.
Export Options
About this article
Cite this article as:
Asakura Tadashi and Ohkawa Kiyoshi, Chemotherapeutic Agents That Induce Mitochondrial Apoptosis, Current Cancer Drug Targets 2004; 4 (7) . https://dx.doi.org/10.2174/1568009043332772
DOI https://dx.doi.org/10.2174/1568009043332772 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Imaging of Abdominal Aortic Aneurysm: The Present and the Future
Current Vascular Pharmacology Mechanisms of Drug Resistance in Cancer Chemotherapy: Coordinated Role and Regulation of Efflux Transporters and Metabolizing Enzymes
Current Pharmaceutical Design Immunossupressant and Organ Transplantation: Immunophilins Targeting Agent and Alternative Therapies
Current Medicinal Chemistry Membrane Fusion and Fission: Enveloped Viruses
Protein & Peptide Letters Combination of Hypoxia and RNA-Interference Targeting VEGF Induces Apoptosis in Hepatoma Cells Via Autocrine Mechanisms
Current Pharmaceutical Biotechnology Tyrosine Kinase Inhibitors (TKIs) in Lung Cancer Treatment: A Comprehensive Analysis
Current Cancer Drug Targets Efficient Growth Inhibition of Human Osteosarcoma Cells Using a Peptide Derived from the MDM-2-Binding Site of p53
Protein & Peptide Letters Nonviral Gene Therapy
Current Gene Therapy Contrast Echocardiography: An Update on Clinical Applications
Current Pharmaceutical Design The Use of Intravenous Aminobisphosphonates for the Treatment of Pagets Disease of Bone
Mini-Reviews in Medicinal Chemistry Recent Progress in Chemically Modified siRNAs
Mini-Reviews in Medicinal Chemistry Amino Acid Degrading Enzymes and their Application in Cancer Therapy
Current Medicinal Chemistry Adaptation of Human and Simian Immunodeficiency Viruses for Resistance to Tetherin/BST-2
Current HIV Research A Very Rare Cerebral Complication of Chemotherapy in a Young Girl: A Difficult Diagnosis
Current Drug Safety Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94
Current Topics in Medicinal Chemistry Vascular Endothelial Cell Growth Factor (VEGF), An Emerging Target for Cancer Chemotherapy
Current Medicinal Chemistry - Anti-Cancer Agents The Use of Lentinan for Treating Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Strategies to Overcome or Circumvent P-Glycoprotein Mediated Multidrug Resistance
Current Medicinal Chemistry The Role of Iron Chelation in Cancer Therapy
Current Medicinal Chemistry Immunotherapy of Human Cancers Using Gene Modified T Lymphocytes
Current Gene Therapy