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作为癌症治疗剂的硒化合物。

Selenium compounds as therapeutic agents in cancer.

作者信息

Fernandes Aristi P, Gandin Valentina

机构信息

Division of Biochemistry, Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.

出版信息

Biochim Biophys Acta. 2015 Aug;1850(8):1642-60. doi: 10.1016/j.bbagen.2014.10.008. Epub 2014 Oct 16.

Abstract

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.

摘要

背景

癌细胞持续产生较高水平的活性氧(ROS),并诱导抗氧化防御以抵消基础ROS产生的增加,肿瘤的储备能力有限,导致一些癌细胞对ROS的脆弱性增加。基于此,氧化应激已被认为是合理设计新型抗癌药物的肿瘤特异性靶点。在氧化还原调节化合物中,硒化合物因其有前景的化疗潜力而备受关注。

综述范围

本综述旨在总结并介绍我们对硒化合物潜在抗癌作用的分子机制的最新认识进展。

主要结论

众所周知,高剂量的硒很容易转变为促氧化剂,从而发挥其潜在的抗癌特性。然而,硒化合物的生物活性及其作用背后的机制高度依赖于其形态以及细胞和组织的特定代谢途径。相反,最相关的无机和有机硒化合物以及硒基纳米颗粒的化学性质和主要分子机制必须予以考虑,并在本文中进行讨论。

普遍意义

阐明并深化我们对硒化合物作用机制的认识将有助于设计和优化具有更特异抗肿瘤特性的化合物,以便未来可能将硒化合物应用于癌症治疗。本文是名为“分化与去分化的氧化还原调节”特刊的一部分。

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