Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 28
Butylated hydroxyanisole is more than a reactive oxygen species scavenger
Nele Festjens1, Michael Kalai1,2, Joél Smet3, Ann Meeus1, Rudy Van Coster3, Xavier
Saelens1,4 and Peter Vandenabeele1
1Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical
Research, Ghent University and Flemish Interuniversity Institute for Biotechnology
(VIB), Technologiepark 927, 9052 Ghent, Belgium; E-mail:
Nele.Festjens@dmbr.Ugent.be
2Laboratory of Cellular Microbiology, Unit of Molecular Microbiology, Institute
Pasteur of Brussels, Engelandstraat 642, 1180 Brussels, Belgium
3Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent
University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
4Molecular Virology Unit, Department for Molecular Biomedical Research, Ghent
University and VIB, Technologiepark 927, 9052 Ghent, Belgium
L929 fibrosarcoma cells treated with TNF or dsRNA die by necrosis, a process in which
mitochondria-produced reactive oxygen species (ROS) are crucial. We studied the effects of
two related chemical antioxidants, butylated hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT). Although they reduced ROS levels similarly, BHA was clearly more
anti-necrotic than BHT, showing that inhibition of necrosis does not exclusively depend on
scavenging ROS. While BHA delays TNF-induced necrosis, it apparently does not block
dsRNA-induced cytotoxicity. However, cell death was shifted from necrosis to apoptosis.
BHT did not modulate cell death type indicating that inhibition of necrotic cell death does not
exclusively depend on scavenging ROS and implying that BHA has additional features
lacking in BHT. We then compared the effects of both antioxidants on the activities of
complexes of the mitochondrial electron transport chain (ETC) with those of specific ETC
inhibitors. BHA is more effective than BHT, but less than rotenone, in the inhibition of
NADH-dehydrogenase activity. However, rotenone is less efficient as anti-necrotic agent,
suggesting that other features of BHA contribute to its protective effect. We finally
demonstrate that phospholipase A2 and lipoxygenases play a role in signalling to or execution
of necrotic cell death. We conclude that the strong anti-necrotic effect of BHA reflects not
only its ROS scavenging property, but also its ability to inhibit complex I and lipoxygenases.
- 361 -