Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy

Dong, L.-F.; Jameson, V.J.A.; Tilly, D.; Procházka, L.; Rohlena, Jakub; Vališ, Karel; Truksa, Jaroslav; Zobalová, Renata; Mandavian, E.; Klučková, Katarína; Stantic, M.; Štursa, Jan; Freeman, R.; Witting, P.K.; Norberg, E.; Goodwin, J.; Salvatore, B.A.; Novotná, Jana; Turánek, J.; Ledvina, Miroslav; Hozák, Pavel; Zhivotovsky, B.; Coster, M.; Ralph, S.J.; Smith, R.A.J.; Neužil, Jiří

doi:https://dx.doi.org/10.1016/j.freeradbiomed.2011.02.032

Number of the records: 1

Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy

1.

SYSNO ASEP	0360075
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy
Author(s)	Dong, L.-F. (AU) Jameson, V.J.A. (NZ) Tilly, D. (AU) Procházka, L. (CZ) Rohlena, Jakub (BTO-N)_{RID, ORCID} Vališ, Karel (BTO-N) Truksa, Jaroslav (BTO-N)_{RID, ORCID} Zobalová, Renata (BTO-N)_RID Mandavian, E. (US) Klučková, Katarína (BTO-N)_RID Stantic, M. (AU) Štursa, Jan (UOCHB-X) Freeman, R. (AU) Witting, P.K. (AU) Norberg, E. (SE) Goodwin, J. (AU) Salvatore, B.A. (US) Novotná, Jana (BTO-N)_RID Turánek, J. (CZ) Ledvina, Miroslav (UOCHB-X)_RID Hozák, Pavel (UMG-J)_{RID, ORCID} Zhivotovsky, B. (SE) Coster, M. (AU) Ralph, S.J. (AU) Smith, R.A.J. (NZ) Neužil, Jiří (BTO-N)_RID
Number of authors	26
Source Title	Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849 Roč. 50, č. 11 (2011), s. 1546-1555
Number of pages	10 s.
Language	eng - English
Country	US - United States
Keywords	Triphenyl phosphonium ; reactive oxygen species ; apoptosis
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GA204/08/0811 GA ČR - Czech Science Foundation (CSF)
	GAP301/10/1937 GA ČR - Czech Science Foundation (CSF)
	IAA500520702 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	KAN200520703 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	KJB500970904 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	KAN200100801 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
CEZ	AV0Z50520701 - BTO-N (2007-2013)
	AV0Z50520514 - UMG-J (2005-2011)
	AV0Z4055905 - UOCHB-X
UT WOS	000290603700010
DOI	10.1016/j.freeradbiomed.2011.02.032
Annotation	Mitochondria are emerging as intriguing targets for anti-cancer agents.We tested here a novel approach,whereby the mitochondrially targeted delivery of anti-cancer drugs is enhanced by the addition of a triphenylphosphonium group (TPP+). A mitochondrially targeted analog of vitamin E succinate (MitoVES),modified by tagging the parental compound with TPP+,induced considerably more robust apoptosis in cancer cells with a 1–2 log gain in anti-cancer activity compared to the unmodified counterpart, while maintaining selectivity for malignant cells.This is because MitoVES associates with mitochondria and causes fast generation of ROS that then trigger mitochondria-dependent apoptosis, involving transcriptional modulation of the Bcl-2 family proteins.MitoVES proved superior in suppression of experimental tumors compared to the untargeted analog. We propose that mitochondrially targeted delivery of anti-cancer agents offers a new paradigm for increasing the efficacy of anti-cancer compounds
Workplace	Institute of Biotechnology
Contact	Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
Year of Publishing	2012

Number of the records: 1