Abstract
Microtubules are composed by α- and β-tubulin polypeptides. α-tubulin undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyrtubulin). Recent studies have shown that α-tubulin tyrosine residues can be nitrated and the incorporation of NO2Tyr into the C-terminus of Glu-tubulin forms a complex that blocks the tyrosination/detyrosination cycle, an event that can compromise protein/enzyme functions, such as cell division. Since many studies demonstrated that Glu-tubulin levels increase in cancer, the aim of the present study was to investigate the effect of new drugs, fluorazone derivatives (K1-K2-K9-K10-K11), on the proliferation of melanoma cells. Our results demonstrated that these drugs, except for K2, were able to inhibit cellular proliferation without exhibiting cytotoxicity. The anti-proliferative effect was accompanied by the decrease of Glu-tubulin levels and the increase of its nitration. This effect seems to be a consequence of NO2 induction and NO2Tyr ligation to Glu-tubulin. Collectively, these results, showing that the fluorazone derivatives, by promoting NO2Tyr incorporation into α-tubulin, are able to arrest the cycle of detyrosination/tyrosination and to inhibit cell proliferation, offer new perspectives for the possible usage of these drugs, alone or in combination, as non-toxic, anti-proliferative agents in melanoma.
Keywords: Cell cycle, cyclin D1, Glu-tubulin, microtubules, nitrotyrosin, skin.
Anti-Cancer Agents in Medicinal Chemistry
Title:Antitubulinic effect of New Fluorazone Derivatives on Melanoma Cells
Volume: 16 Issue: 5
Author(s): Claudia Sticozzi, Francesca Aiello, Rita Bassi Andreasi, Ximena Maria Muresan, Giuseppe Belmonte, Franco Cervellati, Emilia Maellaro, Emanuela Maioli and Giuseppe Valacchi
Affiliation:
Keywords: Cell cycle, cyclin D1, Glu-tubulin, microtubules, nitrotyrosin, skin.
Abstract: Microtubules are composed by α- and β-tubulin polypeptides. α-tubulin undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyrtubulin). Recent studies have shown that α-tubulin tyrosine residues can be nitrated and the incorporation of NO2Tyr into the C-terminus of Glu-tubulin forms a complex that blocks the tyrosination/detyrosination cycle, an event that can compromise protein/enzyme functions, such as cell division. Since many studies demonstrated that Glu-tubulin levels increase in cancer, the aim of the present study was to investigate the effect of new drugs, fluorazone derivatives (K1-K2-K9-K10-K11), on the proliferation of melanoma cells. Our results demonstrated that these drugs, except for K2, were able to inhibit cellular proliferation without exhibiting cytotoxicity. The anti-proliferative effect was accompanied by the decrease of Glu-tubulin levels and the increase of its nitration. This effect seems to be a consequence of NO2 induction and NO2Tyr ligation to Glu-tubulin. Collectively, these results, showing that the fluorazone derivatives, by promoting NO2Tyr incorporation into α-tubulin, are able to arrest the cycle of detyrosination/tyrosination and to inhibit cell proliferation, offer new perspectives for the possible usage of these drugs, alone or in combination, as non-toxic, anti-proliferative agents in melanoma.
Export Options
About this article
Cite this article as:
Sticozzi Claudia, Aiello Francesca, Andreasi Bassi Rita, Muresan Maria Ximena, Belmonte Giuseppe, Cervellati Franco, Maellaro Emilia, Maioli Emanuela and Valacchi Giuseppe, Antitubulinic effect of New Fluorazone Derivatives on Melanoma Cells, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1871520615666150909120014
DOI https://dx.doi.org/10.2174/1871520615666150909120014 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
A Review on Multi-organ Cancer Detection Using Advanced Machine Learning Techniques
Current Medical Imaging Novel Molecular Targets in Cancer Chemotherapy Waiting for Discovery
Current Medicinal Chemistry - Anti-Cancer Agents Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells
Current Medicinal Chemistry Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues
Anti-Cancer Agents in Medicinal Chemistry Unfoldomics of Human Genetic Diseases: Illustrative Examples of Ordered and Intrinsically Disordered Members of the Human Diseasome
Protein & Peptide Letters Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry Up-Regulation of MBD1 Promotes Pancreatic Cancer Cell Epithelial-Mesenchymal Transition and Invasion by Epigenetic Down-Regulation of E-Cadherin
Current Molecular Medicine Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses
Recent Patents on Anti-Cancer Drug Discovery The Role of Ghrelin Signals in Breast Cancer- A Systematic Review
Current Signal Transduction Therapy Tailored Quinolines Demonstrate Flexibility to Exert Antitumor Effects through Varied Mechanisms-A Medicinal Perspective
Anti-Cancer Agents in Medicinal Chemistry Emerging Therapies in Relapsing-Remitting Multiple Sclerosis
Reviews on Recent Clinical Trials Recent Innovations in Antibody-Mediated, Targeted Particulate Nanotechnology and Implications for Advanced Visualisation and Drug Delivery
Current Nanoscience Zebrafish Stem Cell Differentiation Stage Factors Suppress Bcl-xL Release and Enhance 5-Fu-Mediated Apoptosis in Colon Cancer Cells
Current Pharmaceutical Biotechnology Shutting Down the Furnace: Preferential Killing of Cancer Cells with Mitochondrial-Targeting Molecules
Current Medicinal Chemistry Interactions of Dietary Flavonoids with Proteins: Insights from Fluorescence Spectroscopy and Other Related Biophysical Studies
Current Drug Metabolism Targeted Therapies in Metastatic Melanoma: Toward a Clinical Breakthrough?
Anti-Cancer Agents in Medicinal Chemistry Advances in Photodynamic Therapy Assisted by Electroporation
Current Drug Metabolism The Impact of Malnutrition on the Peripheral Serotoninergic System in Anorexia Nervosa: A Systematic Review
Current Psychiatry Reviews The Thyroid Gland: A Crossroad in Inflammation-Induced Carcinoma? An Ongoing Debate with New Therapeutic Potential.
Current Medicinal Chemistry Attacking c-Myc: Targeted and Combined Therapies for Cancer
Current Pharmaceutical Design