金属硫蛋白作为一种自由基清除剂-新的心血管治疗剂或肿瘤耐药引发剂？

Title:Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?

Volume: 17 Issue: 12

Author(s): Zbynek Heger, Miguel Angel Merlos Rodrigo, Sona Krizkova, Branislav Ruttkay-Nedecky, Marta Zalewska, Elena Maria Planells del Pozo, Aurelie Pelfrene, Bertrand Pourrut, Marie Stiborova, Tomas Eckschlager, Gabriella Emri and Rene Kizek and Vojtech Adam

Affiliation:

关键词: 蒽环类抗生素，心血管保护，细胞抗氧化应激，化学耐药性，阿霉素，自由基，金属硫蛋白

摘要: Cardiotoxicity is a serious complication of anticancer therapy by anthracycline antibiotics. Except for intercalation into DNA/RNA structure, inhibition of DNA-topoisomerase and histone eviction from chromatin, the main mechanism of their action is iron-mediated formation of various forms of free radicals, which leads to irreversible damage to cancer cells. The most serious adverse effect of anthracyclines is, thus, cardiomyopathy leading to congestive heart failure, which is caused by the same mechanisms. Here, we briefly summarize the basic types of free radicals formed by anthracyclines and the main processes how to scavenge them. From these, the main attention is paid to metallothioneins. These low-molecular cysteine-rich proteins are introduced and their functions and properties are reviewed. Further, their role in detoxification of metals and drugs is discussed. Based on these beneficial roles, their use as a new therapeutic agent against oxidative stress and for cardioprotection is critically evaluated with respect to their ability to increase chemoresistance against some types of commonly used cytostatics.

Cite this article as:

Zbynek Heger, Miguel Angel Merlos Rodrigo, Sona Krizkova, Branislav Ruttkay-Nedecky, Marta Zalewska , Elena Maria Planells del Pozo, Aurelie Pelfrene, Bertrand Pourrut, Marie Stiborova, Tomas Eckschlager, Gabriella Emri and Rene Kizek and Vojtech Adam , Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?, Current Drug Targets 2016; 17 (12) . https://dx.doi.org/10.2174/1389450116666151001113304