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Cyclophosphamide enhances TNF‐α‐induced apoptotic cell death in murine vascular endothelial cell
Author(s) -
Ohtani Toshio,
Nakamura Tomoyuki,
Toda Ken-ichi,
Furukawa Fukumi
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.092
Subject(s) - apoptosis , programmed cell death , endothelial stem cell , tumor necrosis factor alpha , cyclophosphamide , microbiology and biotechnology , cell , cancer research , chemistry , apoptotic cell death , immunology , biology , medicine , chemotherapy , biochemistry , in vitro
Cyclophosphamide (CPA) is one of the therapeutic agents for systemic inflammatory disorders. In murine dermal endothelial cells (F‐2), 4‐hydroxycyclophosphamide (4‐HC), which is active metabolite of CPA, enhanced TNF‐α‐induced DNA fragmentation. In addition, 4‐HC was shown to elevate TNF‐α‐induced caspase‐3 activation. Caspase‐8 activation was identified by the treatment of TNF‐α, whereas 4‐HC was no effect. In contrast, only when treated with 4‐HC, caspase‐9 activation and the increase in the intracellular expression of Bax were detected. These results suggest that CPA may sensitize endothelial cells to TNF‐α‐induced apoptosis through a mitochondria‐dependent pathway and clinically may contribute to the limitation of inflammatory process.