Osteoblasts activate the Nrf2 signalling pathway in response to arsenic trioxide treatment. (October 2016)

• Record Type: Journal Article
• Authors: Chiu, Pu-Rong; Hu, Yu-Chen; Hsieh, Bau-Shan; Huang, Tzu-Ching; Cheng, Hsiao-Ling; Huang, Li-Wen; Chang, Kee-Lung
• Is Part Of: International journal of biochemistry & cell biology. Volume 79(2016:Oct.)
• Page Start: 327
• Page End: 336
• Publication Date: 2016-10
• Subjects: As arsenic -- ATO arsenic trioxide -- Nrf2 nuclear factor E2 p45-related factor 2 -- HO-1 hemeoxygenase-1 -- HSP heat shock proteins -- HSF heat shock factors -- ZnPPIX protoporphyrin IX zinc (II) -- BSO dl-Buthionine-[S, R]-sulfoximine -- DETC Sodium diethyldithiocarbamate trihydrate -- ROS reactive oxygen species -- DCFH-DA 2′, 7′-dichlorofluorescein-diacetate -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling -- GSH glutathione -- SOD superoxide dismutase -- PARP poly (ADP-ribose) polymerase; Arsenic trioxide -- Osteoblast -- Nrf2 -- Antioxidant -- Heat shock protein; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.08.036
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Abstract: Arsenic trioxide is used to treat a variety of leukaemia types and causes tumour cell death. However, it is not well known whether arsenic trioxide is toxic to bone osteoblast cells, the precursor cells from which leukaemia cells originate. The aim of this study was to examine the response of osteosarcoma cell line MG63 and primary cultured osteoblasts to arsenic trioxide treatment. After 24 h of treatment, arsenic trioxide was more effective at inhibiting cell growth and increasing oxidative stress and DNA damage in MG63 cells than in osteoblasts. In addition, arsenic trioxide arrested cell cycle progression in the G2/M phase, and induced apoptosis in MG63 cells, but not in primary cultured osteoblasts. The results further showed that the expression of transcription factor Nrf2 and its downstream antioxidant effectors, including hemeoxygenase-1, glutathione, and superoxide dismutase, was increased in primary cultured osteoblasts. Additionally, expression of heat shock proteins was also increased. Experiments using inhibitors of antioxidant enzymes in the presence of arsenic trioxide-treated osteoblasts demonstrated that glutathione and superoxide dismutase were responsible for reducing oxidative stress, caspase-3 activity, and apoptosis and that heat shock proteins helped reduce caspase-3 activity. Unexpectedly, there was no apparent effect of the markedly increased hemeoxygenase-1, suggesting that other functions might exist for hemeoxygenase-1. These findings demonstrate that osteosarcoma cells are more sensitive to arsenic trioxide treatment than primary cultured osteoblasts and that primary cultured osteoblasts activate the Nrf2 signalling pathway in response to arsenic trioxide exposure to escape from oxidative damage and apoptosis.