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Selenium compounds as therapeutic agents in cancer
Aristi P Fernandes1, Valentina Gandin2
1Division of Biochemistry, Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Background:
With cancer cells encompassing consistently higher production of reactive oxygen species (ROS) and with an induced antioxidant defense to counteract the increased basal ROS production, tumors have a limited reserve capacity resulting in an increased vulnerability of some cancer cells to ROS. Based on this, oxidative stress has been recognized as a tumor-specific target for the rational design of new anticancer agents. Among redox modulating compounds, selenium compounds have gained substantial attention due to their promising chemotherapeutic potential.
Scope Of Review:
This review aims in summarizing and providing the recent developments of our understanding of the molecular mechanisms that underlie the potential anticancer effects of selenium compounds.
Major Conclusions:
It is well established that selenium at higher doses readily can turn into a prooxidant and thereby exert its potential anticancer properties. However, the biological activity of selenium compounds and the mechanism behind these effects are highly dependent on its speciation and the specific metabolic pathways of cells and tissues. Conversely, the chemical properties and the main molecular mechanisms of the most relevant inorganic and organic selenium compounds as well as selenium-based nanoparticles must be taken into account and are discussed herein.
General Significance:
Elucidating and deepening our mechanistic knowledge of selenium compounds will help in designing and optimizing compounds with more specific antitumor properties for possible future application of selenium compounds in the treatment of cancer. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
Insights
Selenium compounds show promise as anticancer agents by targeting cancer cells' increased reactive oxygen species (ROS) production. Understanding their complex mechanisms, dependent on speciation and metabolism, is key to developing effective cancer therapies.
Area of Science:
- Biochemistry
- Oncology
- Nanotechnology
Background:
- Cancer cells exhibit elevated reactive oxygen species (ROS) and antioxidant defenses, creating a vulnerability exploitable by pro-oxidant therapies.
- Oxidative stress is a tumor-specific target for novel anticancer agent design.
- Selenium compounds are recognized for their significant chemotherapeutic potential due to their redox-modulating properties.
Purpose of the Study:
- To review and summarize recent advancements in understanding the molecular mechanisms of selenium compounds' anticancer effects.
- To discuss the role of selenium speciation, metabolic pathways, and chemical properties in biological activity.
Main Methods:
- Literature review focusing on molecular mechanisms of selenium compounds in cancer.
- Analysis of inorganic and organic selenium compounds, including selenium-based nanoparticles.
- Discussion of redox modulation and oxidative stress in cancer therapy.
Main Results:
- Selenium compounds can act as pro-oxidants at higher doses, exerting anticancer effects.
- The biological activity and anticancer mechanisms of selenium compounds are highly dependent on their speciation and cellular/tissue metabolic pathways.
- Chemical properties and molecular mechanisms vary significantly among different selenium compounds and nanoparticles.
Conclusions:
- Deepening mechanistic knowledge of selenium compounds is crucial for optimizing their antitumor properties.
- Future applications of selenium compounds in cancer treatment depend on designing more specific and effective agents.
- This review contributes to understanding redox regulation in cancer therapy.
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