Apoptosis Induced by Oxaliplatin in Human Colon Cancer HCT15 Cell Line

• Published in: Anticancer research 2004-01, Vol.24 (1), p.219-226
• Main Authors: MARCHETTI, Paolo, GALLA, Domenico A. P, RUSSO, F. Paola, RICEVUTO, Enrico, FLATI, Vincenzo, PORZIO, Giampiero, FICORELLA, Corrado, CIFONE, M. Grazia
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - pathology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Caspases - metabolism; Cell Line, Tumor; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - pathology; Cytochromes c - secretion; Enzyme Activation - drug effects; Fas Ligand Protein; fas Receptor - physiology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Isoenzymes - metabolism; Medical sciences; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - physiology; Membrane Potentials - drug effects; Mitochondria - drug effects; Mitochondria - physiology; Mitochondria - secretion; Organoplatinum Compounds - pharmacology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0250-7005; 1791-7530

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 μM). 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.