Abstract
The sensitivity of cancer cells to apoptosis induced by anticancer drugs in vitro may be a predictor of their sensitivity to these drugs in vivo. In this review I summarize recent data describing anticancer drug-induced apoptosis in human melanoma cells. Proteasome inhibitors alone, or in combination with other drugs, efficiently induce apoptosis in melanoma cells. It has been shown that apoptosis induced by proteasome inhibitors is linked to suppression of transcription factor FoxM1 and upregulation of the proapoptotic Noxa protein. In addition, proteasome inhibitors stabilize the antiapoptotic Mcl-1 protein, and its suppression leads to more robust apoptosis in melanoma cells. Drugs targeting B-Raf (BAY 54-9085) or IKKb (BMS-345541) have been tested in melanoma cell lines, and it has been shown that the proapoptotic activity of both drugs depends on the inhibition of NF-kB in melanoma cells. A synthetic analog of dsRNA in complex with a polycation stimulated autophagy via induction of dsRNA helicase MDA-5 followed by apoptosis that was partially modulated by Noxa. These data may provide important information needed for designing more efficient combinations of anticancer drugs against melanoma.
Keywords: Apoptosis, FOXM1, Noxa, NF-kB, proteasome inhibitors, Mcl-1, ARC, thiostrepton, Malignant melanoma, multiple caspases, mitochondria, endoplasmic reticulum (ER), proapoptotic protein
Current Topics in Medicinal Chemistry
Title: Mechanisms of Apoptosis Induced by Anticancer Compounds in Melanoma Cells
Volume: 12 Issue: 1
Author(s): Andrei L. Gartel
Affiliation:
Keywords: Apoptosis, FOXM1, Noxa, NF-kB, proteasome inhibitors, Mcl-1, ARC, thiostrepton, Malignant melanoma, multiple caspases, mitochondria, endoplasmic reticulum (ER), proapoptotic protein
Abstract: The sensitivity of cancer cells to apoptosis induced by anticancer drugs in vitro may be a predictor of their sensitivity to these drugs in vivo. In this review I summarize recent data describing anticancer drug-induced apoptosis in human melanoma cells. Proteasome inhibitors alone, or in combination with other drugs, efficiently induce apoptosis in melanoma cells. It has been shown that apoptosis induced by proteasome inhibitors is linked to suppression of transcription factor FoxM1 and upregulation of the proapoptotic Noxa protein. In addition, proteasome inhibitors stabilize the antiapoptotic Mcl-1 protein, and its suppression leads to more robust apoptosis in melanoma cells. Drugs targeting B-Raf (BAY 54-9085) or IKKb (BMS-345541) have been tested in melanoma cell lines, and it has been shown that the proapoptotic activity of both drugs depends on the inhibition of NF-kB in melanoma cells. A synthetic analog of dsRNA in complex with a polycation stimulated autophagy via induction of dsRNA helicase MDA-5 followed by apoptosis that was partially modulated by Noxa. These data may provide important information needed for designing more efficient combinations of anticancer drugs against melanoma.
Export Options
About this article
Cite this article as:
L. Gartel Andrei, Mechanisms of Apoptosis Induced by Anticancer Compounds in Melanoma Cells, Current Topics in Medicinal Chemistry 2012; 12 (1) . https://dx.doi.org/10.2174/156802612798919196
DOI https://dx.doi.org/10.2174/156802612798919196 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery Subject Index To Volume 6
Current Molecular Medicine The Molecular Targets of Cannabinoids in the Treatment of Cancer and Inflammation
Current Pharmaceutical Design Dendritic Cell/NK Cell Interaction in RNA Virus Infection
Current Immunology Reviews (Discontinued) Drug Resistance: Challenges to Effective Therapy
Current Cancer Drug Targets Repurposing Drugs for Cancer Prevention
Current Topics in Medicinal Chemistry PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration
Current Alzheimer Research Lentiviral Vectors for Anti-Tumor Immunotherapy
Current Gene Therapy The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell
Current Pharmaceutical Design CYP17 Inhibitors for Prostate Cancer Treatment – An Update
Current Medicinal Chemistry Anticancer Drugs Targeting the Apoptotic Pathway
Medicinal Chemistry Reviews - Online (Discontinued) Effect of Flavonoids on Human Health: Old Subjects but New Challenges
Recent Patents on Biotechnology Charge Deficient Analogues of the Natural Polyamines
Current Pharmaceutical Design dUTPase in Human Neoplastic Cells as a Potential Target for Therapeutic Intervention
Current Protein & Peptide Science Ultrasonic and Microwave Assisted Synthesis of Nitrogen-Containing Derivatives of Juglone as Potential Antibacterial Agents
Letters in Organic Chemistry Emerging Therapeutic Strategies for Rheumatoid Arthritis
Current Drug Therapy The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Exosomes Harnessed as Nanocarriers for Cancer Therapy - Current Status and Potential for Future Clinical Applications
Current Molecular Medicine Prospects of Nanocarriers for Oral Delivery of Bioactives Using Targeting Strategies
Current Pharmaceutical Biotechnology The Immune System of Cancer Patients
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry