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The influence of 4‐hydroxy‐2‐nonenal on proliferation, differentiation and apoptosis of human osteosarcoma cells
Author(s) -
Sunjic Suzana Borovic,
Cipak Ana,
Rabuzin Filip,
Wildburger Renate,
Zarkovic Neven
Publication year - 2005
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520240117
Subject(s) - apoptosis , dapi , mitosis , cell growth , osteosarcoma , alkaline phosphatase , cellular differentiation , microbiology and biotechnology , osteoblast , cell , programmed cell death , chemistry , biology , cancer research , biochemistry , in vitro , gene , enzyme
The product of lipid peroxidation, 4‐hydroxy‐2‐nonenal (HNE) is known to cause cell death at high concentrations, while at lower concentrations it can influence cell proliferation and differentiation. In our experiments we used human osteosarcoma cells (HOS), to test the influence of HNE on cell proliferation, differentiation and induction of apoptosis. Apoptosis induction was estimated by TiterTACS™ TUNEL test. The cells were in parallel counted and the DAPI staining method was used to distinguish between apoptotic and necrotic cells as well as to define the proportion of cells in mitosis. To test the influence of HNE on HOS cell differentiation, cells were treated every second day with HNE. After 10 days, the cells were stained for alkaline phosphatase, a marker for osteoblast differentiation. Cell growth inhibition was caused by supraphysiological concentrations of 10 or 100 μM HNE, while apoptosis was induced with supraphysiological as well as by the physiological amount of the aldehyde (1 μM). Necrosis appeared when cells were treated with 10 or 100 μM, but not with 1 μM HNE. The proportion of cells in mitosis gradually declined with increased HNE concentration. Multiple exposures of HOS cells to 10 μM HNE prevented HOS cell differentiation. These results indicated that HNE inhibits proliferation and differentiation of HOS cells in the same concentration dependent manner as it causes apoptosis. We thus assume that HNE might be one of the important signaling molecules regulating the growth of the human osteosarcoma cells.