Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 67, Issue 5, Pages 807-816Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0212-2
Keywords
Neuroblastoma; Fenretinide; Mitochondrial respiratory chain; Reactive oxygen species; MitoQ; Trolox
Categories
Funding
- Stichting Kindergeneeskundig Kankeronderzoek (SKK) of The Netherlands
Ask authors/readers for more resources
Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demonstrated by detection of superoxide with MitoSOX, the scavenging effect of the mitochondrial antioxidant MitoQ and reduced ROS production in cells without a functional mitochondrial respiratory chain (Rho zero cells). In digitonin-permeabilized cells, a fenretinide concentration-dependent decrease in ATP synthesis and substrate oxidation was observed, reflecting inhibition of the mitochondrial respiratory chain. However, inhibition of the mitochondrial respiratory chain was not required for ROS production. Co-incubation of fenretinide with inhibitors of different complexes of the respiratory chain suggested that fenretinide-induced ROS production occurred via complex II. The cytotoxicity of fenretinide was exerted through the generation of mitochondrial ROS and, at higher concentrations, also through inhibition of the mitochondrial respiratory chain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available