Original scientific paper
Growth Modulation of Human Cells in Vitro by Mild Oxidative Stress and 1,4-Dihydropyridine Derivative Antioxidants
Tomislava Lovaković
Marija Poljak-Blazi
Gunars Duburs
Ana Cipak
Marina Cindrić
Brigita Vigante
Egils Bisenieks
Morana Jaganjac
Lidija Mrakovčić
Azra Dedić
Neven Žarković
Abstract
Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction
in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects
of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were
analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation.
The cells were pretreated with either cerebrocrast or Z41-74 and afterwards exposed to mild, copper induced lipid peroxidation
or to 4-hydroxynonenal (HNE), the end product of lipid peroxidation. The results obtained have shown that
both antioxidants exert growth modulating effects interfering with the lipid peroxidation. Namely, cells treated with antioxidants
showed increased metabolic rate and cell growth, thereby attenuating the effects of lipid peroxidation. Such
biomodulating effects of cerebrocrast and Z41-74 resembled growth modulating effects of HNE, suggesting that the antioxidants
could eventually promote cellular adaptation to oxidative stress interacting with redox signaling and hydroxynonenal
HNE-signal transduction pathways. This may be of particular relevance for better understanding the beneficial
role of hydroxynonenal HNE in cell growth control. Therefore, cerebrocrast and Z41-74 could be convenient to study further
oxidative homeostasis involving lipid peroxidation.
Keywords
oxidative homeostasis; growth regulation; hormesis; reactive aldehydes; HNE; bone cells
Hrčak ID:
64764
URI
Publication date:
7.3.2011.
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