Abstract
The history of metal based cytostatics began in the 1970s by discovering the effects of cisplatin. Since then several generations of platinum based cytostatics have started to be the key weapon against tumor development and metastasis occurrence. Nevertheless, some attention has been also paid to non-platinum metals, such as ruthenium, titanium, gallium, iron, cobalt, gold, and palladium. Ruthenium, titanium, and gallium complexes have been also tested in clinical studies. This boom in metal based cytostatics can be explained by great effort paid to the elucidation of mechanisms of tumor resistance to these drugs. The known mechanisms of drug resistance are: (i) down regulation, over-expression, or modification of molecules of interest; (ii) increased drug efflux; (iii) induction of anti-apoptotic mechanisms or inactivation of pro-apoptotic mechanisms; (iv) changes in enzymes with an ability to activate or detoxify a drug; (v) low access of the drug to a tumor; and/or (vi) alteration in drug metabolism or excretion [1]. Often discussed but not largely reviewed and summarized is the intracellular inactivation of platinum drugs by coordination to thiol containing biomolecules glutathione (GSH) and metallothioneins (MTs). Overexpression of MT and/or GSH may cause resistance to anticancer drugs. Thus, greater attention should be paid to these interactions in case to overcome the resistance of tumor to cytostatics.
Keywords: Metal-containing cytostatic drugs, platinum, resistance, chemoresistance, glutathione, metallothioneins.
Anti-Cancer Agents in Medicinal Chemistry
Title:Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Volume: 16 Issue: 6
Author(s): Jan Hrabeta, Vojtech Adam, Tomas Eckschlager, Eva Frei, Marie Stiborova and Rene Kizek
Affiliation:
Keywords: Metal-containing cytostatic drugs, platinum, resistance, chemoresistance, glutathione, metallothioneins.
Abstract: The history of metal based cytostatics began in the 1970s by discovering the effects of cisplatin. Since then several generations of platinum based cytostatics have started to be the key weapon against tumor development and metastasis occurrence. Nevertheless, some attention has been also paid to non-platinum metals, such as ruthenium, titanium, gallium, iron, cobalt, gold, and palladium. Ruthenium, titanium, and gallium complexes have been also tested in clinical studies. This boom in metal based cytostatics can be explained by great effort paid to the elucidation of mechanisms of tumor resistance to these drugs. The known mechanisms of drug resistance are: (i) down regulation, over-expression, or modification of molecules of interest; (ii) increased drug efflux; (iii) induction of anti-apoptotic mechanisms or inactivation of pro-apoptotic mechanisms; (iv) changes in enzymes with an ability to activate or detoxify a drug; (v) low access of the drug to a tumor; and/or (vi) alteration in drug metabolism or excretion [1]. Often discussed but not largely reviewed and summarized is the intracellular inactivation of platinum drugs by coordination to thiol containing biomolecules glutathione (GSH) and metallothioneins (MTs). Overexpression of MT and/or GSH may cause resistance to anticancer drugs. Thus, greater attention should be paid to these interactions in case to overcome the resistance of tumor to cytostatics.
Export Options
About this article
Cite this article as:
Hrabeta Jan, Adam Vojtech, Eckschlager Tomas, Frei Eva, Stiborova Marie and Kizek Rene, Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (6) . https://dx.doi.org/10.2174/1871520616666151120122611
DOI https://dx.doi.org/10.2174/1871520616666151120122611 |
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
-
Redox Homeostasis, Bioactive Agents and Transduction Therapy
Current Signal Transduction Therapy Exploring a Novel Target Treatment on Breast Cancer: Aloe-emodin Mediated Photodynamic Therapy Induced Cell Apoptosis and Inhibited Cell Metastasis
Anti-Cancer Agents in Medicinal Chemistry Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Drugs Made of RNA: Development and Application of Engineered RNAs for Gene Therapy
Mini-Reviews in Medicinal Chemistry Anti-cancer and Anti-angiogenic Properties of Various Natural Pentacyclic Tri-terpenoids and Some of their Chemical Derivatives
Current Organic Chemistry Disulfiram's Anticancer Activity: Evidence and Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Microgravity Alters Cancer Growth and Progression
Current Cancer Drug Targets Preclinical Investigation of Radiopharmaceuticals: An Accurate and Multidisciplinary Approach
Current Radiopharmaceuticals HLA Class I Expression, Tumor Escape and Cancer Progression
Current Cancer Therapy Reviews Recent Patents of DNA Methylation Biomarkers in Gastrointestinal Oncology
Recent Patents on DNA & Gene Sequences Optimising the Azeotropic Drying of 18F-Fluorine Wayto Improve the 18F-Fluorocholine Radiochemical Yield
Current Radiopharmaceuticals Choline Kinase Alpha Depletion Selectively Kills Tumoral Cells
Current Cancer Drug Targets Pharmacogenomics of Cytochrome P450 Enzymes in Tumours
Current Pharmacogenomics Nanomedicines as Cancer Therapeutics: Current Status
Current Cancer Drug Targets Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies
Current Pharmaceutical Design New Approach to Cancer Therapy: The Application of Signal Transduction to Anti-Cancer Drug
Current Medicinal Chemistry - Anti-Cancer Agents Interleukin 2 in Cancer Therapy
Current Medicinal Chemistry Signaling Through Rho GTPase Pathway as Viable Drug Target
Current Medicinal Chemistry