title: Different patterns of apoptosis in response to cisplatin in B50 neuroblastoma rat cells.
abstract: Cisplatin (cisPt) is a chemotherapeutic drug used for several human malignancies. CisPt cytotoxicity is primarily mediated by its ability to cause DNA damage and subsequent apoptotic cell death. DNA is the primary target of cisPt; however, recent data have shown that cisPt may have important direct interactions with mitochondria, which can induce apoptosis and may account for a significant part of the clinical activity associated with this drug. We have previously demonstrated that in the rat neuronal cell line B50, at 20 h-treatment with cisPt activates apoptosis through an intrinsic pathway involving an alteration of mitochondrial membrane permeability and the release of cytochrome c. The present study investigates different death pathways induced in the same cell line by a prolonged treatment with 40 µM cisPt for 48 h. To address this issue, we focused on caspases-8 and -12, and on the mitochondrial apoptosis inducing factor (AIF), which translocates to the nucleus and induces cell death via caspase-independent pathway. We found that cisPt activates different forms of cell death, i.e. the receptor-mediated apoptotic extrinsic pathway and a death process mediated by endoplasmic reticulum stress. Moreover, we demonstrated that AIF-mediated death occurs, being characterized by the translocation of AIF from mitochondria to the nucleus. On the whole, we provided evidence that prolonged cisPt treatment is able to activate both caspase-dependent and caspase-independent apoptotic pathways in B50 rat neuronal cells.
authors.affiliation: Department of Animal Biology, Laboratory of Cell Biology and Neurobiology, University of Pavia, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Santin
authors.forename: V M
authors.initials: VM
authors.lastname: Piccolini
authors.forename: P
authors.initials: P
authors.lastname: Veneroni
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: G
authors.initials: G
authors.lastname: Bernocchi
authors.forename: M G
authors.initials: MG
authors.lastname: Bottone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: C494831:Aifm1 protein, rat; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; C505410:Casp3 protein, rat; D053148:Caspase 3; D002945:Cisplatin