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. MATERIALS AND 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. CONCLUSION: 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.

Apoptosis induced by oxaliplatin in human colon cancer HCT15 cell line

RICEVUTO, Enrico;FLATI, VINCENZO;PORZIO, Giampiero;FICORELLA, Corrado;CIFONE, MARIA GRAZIA
2004

Abstract

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. MATERIALS AND 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. CONCLUSION: 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/1384
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