Increased Expression of Death Receptors 4 and 5 Synergizes the Apoptosis Response to Combined Treatment with Etoposide and TRAIL

CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors

“…While being consistent with previous reports demonstrating that DR5 expression is upregulated following treatment with DNA-damaging agents (Gibson et al, 2000), our work also demonstrates the existence of the smaller 32 kDa band. While the exact relationship between the 32 kDa band and the full-length 58 kDa band remains to be elucidated, one potential explanation from our work would be that the smaller band represents a precursor form of DR5.…”

“…Besides our demonstration of the existence of the 32 kDa band, our work also reveals a functional relationship between caspase-9 and DR5. Previous work has indicated that death signals related with DR5 are subsequently transmitted downstream to caspase-9 processing events (Gibson et al, 2000). However, our findings suggest that caspase-9 processing also affects DR5 expression following drug-induced DNA damage, since pretreatment with the caspase-9 inhibitor z-LEHD-fmk negatively affects expression levels of both the 58 and 32 kDa bands in topoisomerase II inhibitor-treated cells.…”

“…Caspase-9-dependent involvement of DR5 in etoposideinduced apoptosis in CD26 Jurkat transfectants Expression of death receptor 5 (DR5), a member of the TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) family, is upregulated following treatment with such DNA-damaging agents as doxorubicin and etoposide (Gibson et al, 2000). We now demonstrate that etoposide treatment leads to a greater increase in the levels of the 58 kDa DR5 in wtCD26 transfectants as compared with S630A or parental Jurkat cells ( Figure 8A).…”

Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy

“…Several reports Desjosez et al, 2000;Gibson et al, 2000;Nagane et al, 2000;Yamanaka et al, 2000;Lacour et al, 2001;Mizutani et al, 2001), including our own , have demonstrated that chemotherapeutic drugs augment Apo2L/TRAIL-induced apoptosis of sensitive, and more importantly Apo2L/TRAIL-resistant, cancer cells. Experiments were performed to determine whether combinations of Apo2L/TRAIL with chemotherapeutic agents clinically relevant for the treatment of osteosarcoma, including DOX, CDDP or ETP, could reverse the acquired resistance to Apo2L/TRAIL.…”

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

“…These results further our understanding of the early molecular mechanism responsible for the induction of apoptosis by CD437 in ovarian carcinoma cells and map the activation of p38 directly to the activation of MEK (Holmes et al, 2003b). We have already determined that c-RAF is not the upstream activator of MEK but recent reports have shown MEKK1, an upstream activator of MEK, to be necessary for apoptosis induced by cisplatin and TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) so it is possible that activation of MEK by CD437 may be through the MEKK1/SEK1 pathway (Gibson et al, 2000;Bild et al, 2002;Sanchez-Perez et al, 2002).…”