DDTD, an isoflavone derivative, induces cell apoptosis through the reactive oxygen species/apoptosis signal-regulating kinase 1 pathway in human osteosarcoma cells
In: European Journal of Pharmacology, Jg. 597 (2008-11-12), Heft 1-3, S. 19-26
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Zugriff:
Abstract: Osteosarcoma is the most common primary bone tumor associated with childhood and adolescence. In the present study, we investigated the anticancer effect of a new isoflavone derivative, 3′,4′-dichloro-3-(3,4-dichlorophenylacetyl)-2,4,6-trihydroxydeoxybenzoin (DDTD) in human osteosarcoma cells. DDTD induced cell apoptosis in human osteosarcoma cell lines (including: U2OS, MG-63, Saos2 and ROS 17/2.8). We found that the accumulation of reactive oxygen species is a critical mediator in DDTD-induced cell death. DDTD induced apoptosis signal-regulating kinase 1 (ASK1) dephosphorylation and its dissociation from 14-3-3. Treatment of osteosarcoma cells with DDTD induced p38 and p53 phosphorylation. Transfection with ASK1, mitogen activated protein kinase (MAPK) kinase (MKK)3/6, and p38 small interfering RNA (siRNA) antagonized the DDTD-induced cell apoptosis. DDTD also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio and Caspase-9 activation. Bax knockdown using a Bax siRNA strategy reduced Bax expression and subsequent cell death. In addition, transfection of cells with ASK1, MKK3/6, and p38 siRNA reduced DDTD-induced p38 activation, p53 phosphorylation and Bax expression. These results suggest that DDTD generates reactive oxygen species and activates the ASK1–MKK3/6–p38–p53–Bax pathway to cause osteosarcoma cell death. [Copyright &y& Elsevier]
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DDTD, an isoflavone derivative, induces cell apoptosis through the reactive oxygen species/apoptosis signal-regulating kinase 1 pathway in human osteosarcoma cells
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Autor/in / Beteiligte Person: | Chen, Jung-Tsan ; Fong, Yi-Chin ; Li, Te-Mao ; Liu, Ju-Fang ; Hsu, Che-Wei ; Chang, Chih-Shiang ; Tang, Chih-Hsin |
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Zeitschrift: | European Journal of Pharmacology, Jg. 597 (2008-11-12), Heft 1-3, S. 19-26 |
Veröffentlichung: | 2008 |
Medientyp: | academicJournal |
ISSN: | 0014-2999 (print) |
DOI: | 10.1016/j.ejphar.2008.08.036 |
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