http://www.cnr.it/ontology/cnr/individuo/prodotto/ID297123

Mitochondria-targeted Resveratrol Derivatives Act as Cytotoxic Pro-oxidants (Articolo in rivista)

Type

Label

Mitochondria-targeted Resveratrol Derivatives Act as Cytotoxic Pro-oxidants (Articolo in rivista) (literal)

Anno

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

Alternative label

Sassi, Nicola; Mattarei, Andrea; Azzolini, Michele; Bernardi, Paolo; Szabo, Ildiko'; Paradisi, Cristina; Zoratti, Mario; Biasutto, Lucia (2014)
Mitochondria-targeted Resveratrol Derivatives Act as Cytotoxic Pro-oxidants
in Current pharmaceutical design (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Sassi, Nicola; Mattarei, Andrea; Azzolini, Michele; Bernardi, Paolo; Szabo, Ildiko'; Paradisi, Cristina; Zoratti, Mario; Biasutto, Lucia (literal)

Pagina inizio

Pagina fine

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

Rivista

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

Note

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

University of Padua; Consiglio Nazionale delle Ricerche (CNR); University of Padua; University of Padua (literal)

Titolo

Mitochondria-targeted Resveratrol Derivatives Act as Cytotoxic Pro-oxidants (literal)

Abstract

Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low mu M range. Resveratrol is essentially without effect under these experimental conditions, while the cytotoxicity of the mitochondriotropic derivatives increases if they are methylated on the remaining hydroxyls. Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active \"mitocans\", whose mechanisms of action and in vivo activity are worthy of further investigation. (literal)

Prodotto di