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
-
Carbohydrate-Metal Complexes and their Potential as Anticancer Agents
Current Medicinal Chemistry Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry Benzothiazole: A Versatile and Multitargeted Pharmacophore in the Field of Medicinal Chemistry
Letters in Organic Chemistry Fibroblast Growth Factor-Inducible 14: Multiple Roles in Tumor Metastasis
Current Molecular Medicine Molecular Aspects of Stromal-Parenchymal Interactions in Malignant Neoplasms
Current Molecular Medicine Clinical Importance and Potential Use of Small Molecule Inhibitors of Focal Adhesion Kinase
Anti-Cancer Agents in Medicinal Chemistry The Immunohistochemical Expression of the E-Cadherin, Alpha-Catenin,Beta-Catenin and Gamma Catenin Proteins in Epithelial Ovarian Tumours: Relationship with Clinicopathologic Parameters and Patient Survival
Current Women`s Health Reviews Advancement Towards Tin-based Anticancer Chemotherapeutics: Structural Modification and Computer Modeling Approach to Drug-Enzyme Interactions
Current Topics in Medicinal Chemistry Ribozymes in the Age of Molecular Therapeutics
Current Molecular Medicine Promotion of Apoptosis in Cancer Cells by Selective Purine-Derived Pharmacological CDK Inhibitors: One Outcome, Many Mechanisms
Current Pharmaceutical Design New Insights in the Gene Electrotransfer Process: Evidence for the Involvement of the Plasmid DNA Topology
Current Gene Therapy Insulin Decreases Therapeutic Efficacy in Colon Cancer Cell Line HT29 Via the Activation of the PI3K/Akt Pathway
Current Drug Discovery Technologies 2',6'-dihydroxy-4'-methoxy Dihydrochalcone Improves the Cognitive Impairment of Alzheimer's Disease: A Structure-activity Relationship Study
Current Topics in Medicinal Chemistry Modified Nucleosides That Can Be Incorporated into DNA Enzymatically or in Live Cells
Current Organic Chemistry Photodynamic Therapy in Melanoma - Where do we Stand?
Current Medicinal Chemistry The Applicability of mTOR Inhibition in Solid Tumors
Current Cancer Drug Targets Meet Our Editorial Board Member
Current Drug Delivery Hepatoma-Derived Growth Factor in Carcinogenesis and Cancer Progression
Current Drug Therapy DNA Methylation Based Biomarkers in Non-Invasive Cancer Screening
Current Molecular Medicine Regulation of Female Fertility and Identification of Future Contraceptive Targets
Current Pharmaceutical Design