Involvement of C-jun NH2-terminal kinase and apoptosis induced factor in apoptosis induced by deglycosylated bleomycin in laryngeal carcinoma cells.
In our previous studies, we demonstrated that the deglycosylation of bleomycin-A2 (BLM-A2) does not affect the capacity of this drug to induce cell death by apoptosis in a caspase-independent manner in laryngeal cancer cells (HEp-2), but suppresses the ability of BLM-A2 to induce ROS formation. We have now investigated the consequence of BLM-A2 deglycosylation in terms of the involvement of apoptotic pathways in HEp-2 cells. Apoptosis induced by bleomycin-A2 and deglyco-BLM-A2 is associated with the release of cytochrome c and AIF. Only Bax was oligomerized with BLM-A2-induced HEp-2 cell death. BLM-A2 and deglyco-BLM-A2-induced apoptosis depended on JNK activation but was independent of death receptors expression. In contrast, both of these drugs would sensitize HEp-2 cells to death receptor ligand-induced cell death. These observations indicate that the deglycosylation of BLM does not impair the ability of the drug to trigger cell death through activation of the intrinsic pathway by the release of AIF responsible for mitochondrial permeability and chromatin condensation independent of caspases activation.
Brahim
Souhir
S
Department of Science, Laboratory of Biochemistry UR09/09. Faculty of Medicine, 5019 Monastir, Tunisia.
Aroui
Sonia
S
Abid
Kaouthar
K
Kenani
Abderraouf
A
D000873:Anthracenes / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000187:drug effects / Q000378:metabolism*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002277:Carcinoma / Q000201:enzymology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000201:enzymology*; D007938:Leukemia / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
C494829:AIFM1 protein, human; D000873:Anthracenes; D000903:Antibiotics, Antineoplastic; D051033:Apoptosis Inducing Factor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D001761:Bleomycin; C432165:pyrazolanthrone; C033284:deglycobleomycin; D048031:JNK Mitogen-Activated Protein Kinases