Apoptosis induced by oxaliplatin in human colon cancer HCT15 cell line.
BACKGROUND
Oxaliplatin (L-OHP), active in a wide range of human and animal tumours, also CDDP-resistant, possesses unique molecular characteristics of action. However, the mechanisms by which the damage induced by L-OHP triggers a death signal are not yet fully defined.


METHODS
After L-OHP treatment of the HCT15 human colon cancer cell line, apoptosis was evaluated by DNA laddering detection and by flow cytometry; the effect on specific caspase-3, -8 and -9 inhibitors, mitochondrial membrane permeability transition, cytochrome C release and expression of CD95 and CD95L were also assessed.


RESULTS
HCT15 cells underwent apoptosis when treated with all used drug concentrations (7-25 microM). Treatment of cells with L-OHP resulted in the activation of caspase-8, -9 and -3, in a mitochondrial membrane depolarisation, and in an increase of CD95 receptor and CD95 ligand levels.


CONCLUSIONS
The results correlated well with the ability of L-OHP to induce apoptosis and give further insights into the mechanisms underlying the L-OHP-induced apoptosis of tumor cells.
Marchetti
Paolo
P
Department of Experimental Medicine, University of L'Aquila, Via Vetoio 10, Coppito 2, 67100 L'Aquila, Italy. paolo.marchetti@aquila.infn.it
Galla
Domenico A P
DA
Russo
F Paola
FP
Ricevuto
Enrico
E
Flati
Vincenzo
V
Porzio
Giampiero
G
Ficorella
Corrado
C
Cifone
M Grazia
MG
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D019014:fas Receptor / Q000502:physiology
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009944:Organoplatinum Compounds; D019014:fas Receptor; D000077150:Oxaliplatin; D045304:Cytochromes c; D020169:Caspases