Interactions of vitamin D analogue CB1093, TNFα and ceramide on breast cancer cell apoptosis

摘要: Abstract Mechanisms by which vitamin D analogues promote apoptosis in tumour cells are unclear. In this study we have examined possible interactions between the synthetic analogue CB1093 and two other known mediators of apoptosis, TNFα ceramide, MCF-7, T47D Hs578T breast cancer cells. These studies indicated that cytosolic phospholipase A2 (cPLA2) is involved as well TNFα-mediated cell death. promoted both ceramide-induced c-PLA2 activation, was inversely related to loss viability MCF-7 alone (5–20 ng/ml) failed induce cytotoxicity activation cPLA2 However, pretreatment these with potentiated C2-ceramide-induced Treatment induced DNA fragmentation all three lines 5 days effects were accompanied cPLA2. Furthermore, co-treatment inhibitor AACOCF3 led partial protection against The broad-spectrum caspase z-VAD-fmk prevented but not C2-ceramide CB1093-mediated release arachidonic acid death results indicate potentiates responsiveness suggest ceramide and/or might be downstream effectors D-mediated caspase-independent