title: Differential sensitivity to 4-hydroxynonenal for normal and malignant mesenchymal cells.
abstract: Normal and malignant cells of various origin differ in their sensitivity to oxidative stress. Therefore, we used normal and malignant mesenchymal cells--human osteosarcoma cells (HOS and 143B), human fibroblasts (WI38) and two primary cultures of normal human osteoblasts to test sensitivity to reactive aldehyde 4-hydroxynonenal (HNE), known as a second messenger of free radicals and a signaling molecule. Upon HNE-treatment, decrease in cell viability (by Trypan-blue), apoptosis induction (by TiterTACS TUNEL assay), HNE-protein binding (by HNE-His ELISA) were higher in malignant than in normal cells, while glutathione content was higher in normal cells. These results indicate that HNE affects the growth of malignant mesenchymal cells more than normal and that this effect was mainly related to lower glutathione concentration and higher binding of HNE to the cellular proteins. We thus assume that HNE and GSH homeostasis play an important role in the growth regulation of normal and malignant mesenchymal cells.
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia. borovic@irb.hr
authors.forename: Suzana
authors.initials: S
authors.lastname: Borovic
authors.forename: Ana
authors.initials: A
authors.lastname: Cipak
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Kejla
authors.forename: Darko
authors.initials: D
authors.lastname: Perovic
authors.forename: Georg
authors.initials: G
authors.lastname: Waeg
authors.forename: Neven
authors.initials: N
authors.lastname: Zarkovic
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values
chemical_list: D000447:Aldehydes; D009363:Neoplasm Proteins; D011506:Proteins; C027576:4-hydroxy-2-nonenal