title: Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
abstract: 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.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Heger
authors.forename: Miguel Angel Merlos
authors.initials: MA
authors.lastname: Rodrigo
authors.forename: Sona
authors.initials: S
authors.lastname: Krizkova
authors.forename: Branislav
authors.initials: B
authors.lastname: Ruttkay-Nedecky
authors.forename: Marta
authors.initials: M
authors.lastname: Zalewska
authors.forename: Elena Maria Planells
authors.initials: EM
authors.lastname: Del Pozo
authors.forename: Aurelie
authors.initials: A
authors.lastname: Pelfrene
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pourrut
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborova
authors.forename: Tomas
authors.initials: T
authors.lastname: Eckschlager
authors.forename: Gabriella
authors.initials: G
authors.lastname: Emri
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic. vojtech.adam@mendelu.cz.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000209:etiology* / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008668:Metallothionein / Q000378:metabolism / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D008668:Metallothionein