Cell proliferation, apoptosis and mitochondrial damage in rat B50 neuronal cells after cisplatin treatment.
OBJECTIVE
Cisplatin (cisPt) is used as a chemotherapeutic agent for the treatment of a variety of human tumours; more recently, it has been demonstrated that tumour cell exposure to cisPt ultimately results in apoptosis, but the mechanism by which nuclear cisPt/DNA generates the cytoplasmic cascade of events involved has not been clarified. We have investigated the effects of cisPt on proliferation in the neuronal cell line B50, with particular attention being given to understand whether mitochondria are a target of cisPt and their involvement in the apoptotic process.


METHODS
Rat neuronal B50 cells were used to investigate the mechanisms of cisPt-induced cytotoxicity; this line has been used as a model system for neurotoxicity in vivo.


RESULTS
Changes in proliferation, induction of apoptosis, activation of caspase-3 and DNA fragmentation were observed in the cells, as well as morphological and biochemical alterations of mithocondria. Activation of caspase-9 confirmed that mitochondria are a target of cisPt.


CONCLUSIONS
CisPt exerts cytotoxic effects in the neuronal B50 cell line via a caspase-dependent pathway with mitochondria being central relay stations.
Bottone
M G
MG
Dipartimento di Biologia Animale, Università di Pavia, and Istituto di Genetica Moleculare, Sezione di Istochimica e Citochimica del CNR, Pavia, Italy. bottone@unipv.it
Soldani
C
C
Veneroni
P
P
Avella
D
D
Pisu
M
M
Bernocchi
G
G
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D011419:Propidium / Q000378:metabolism; D051381:Rats
D017304:Annexin A5; D011419:Propidium; D053453:Caspase 9; D001973:Bromodeoxyuridine; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin