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. © 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
Ohtani, T., Nakamura, T., Toda, K. I., & Furukawa, F. (2006). Cyclophosphamide enhances TNF-α-induced apoptotic cell death in murine vascular endothelial cell. FEBS Letters, 580(6), 1597–1600. https://doi.org/10.1016/j.febslet.2006.01.092