title: Growth modulation of human cells in vitro by mild oxidative stress and 1,4-dihydropyridine derivative antioxidants.
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.
authors.affiliation: J J Strossmayer University, Department of Biology, Osijek, Croatia.
authors.forename: Tomislava
authors.initials: T
authors.lastname: Lovaković
authors.forename: Marija
authors.initials: M
authors.lastname: Poljak-Blazi
authors.forename: Gunars
authors.initials: G
authors.lastname: Duburs
authors.forename: Ana
authors.initials: A
authors.lastname: Cipak
authors.forename: Marina
authors.initials: M
authors.lastname: Cindrić
authors.forename: Brigita
authors.initials: B
authors.lastname: Vigante
authors.forename: Egils
authors.initials: E
authors.lastname: Bisenieks
authors.forename: Morana
authors.initials: M
authors.lastname: Jaganjac
authors.forename: Lidija
authors.initials: L
authors.lastname: Mrakovcić
authors.forename: Azra
authors.initials: A
authors.lastname: Dedić
authors.forename: Neven
authors.initials: N
authors.lastname: Zarković
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D019327:Copper Sulfate / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D004095:Dihydropyridines; D017382:Reactive Oxygen Species; C073838:2,6-dimethyl-3,5-bis(2'-propoxyethoxycarbonyl)-4-(2''-difluoromethoxyphenyl)-1,4-dihydropyridine; C038806:1,4-dihydropyridine; C027576:4-hydroxy-2-nonenal; D019327:Copper Sulfate