Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death

• Published in: Cancer letters Vol. 287; no. 2; pp. 216 - 223
• Main Authors: Martín, Vanesa, García-Santos, Guillermo, Rodriguez-Blanco, Jezabel, Casado-Zapico, Sara, Sanchez-Sanchez, Ana, Antolín, Isaac, Medina, Maria, Rodriguez, Carmen
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.01.2010; Elsevier Limited
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Cancer therapies; Cell death; Cell growth; Cell Line, Tumor; Cell Survival - drug effects; Death receptors; Glioma; Glioma - metabolism; Glioma - pathology; Hematology, Oncology and Palliative Medicine; Humans; Inhibitor of Apoptosis Proteins; Melatonin; Melatonin - pharmacology; Microtubule-Associated Proteins - metabolism; Phosphorylation; Protein Kinase C - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Signal Transduction - drug effects; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL; Tumors; Melatonin; TRAIL; Glioma; Death receptors; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2009.06.016

Abstract Despite the common expression of death receptors, many types of cancer including gliomas are resistant to the death receptor ligand (TRAIL). Melatonin antitumoral actions have been extensively described, including oncostatic properties on several tumor types and improvement of chemotherapeutic regimens. Here, we found that melatonin effectively increase cell sensitivity to TRAIL-induced cell apoptosis in A172 and U87 human glioma cells. The effect seems to be related to a modulation of PKC activity which in turns decreases Akt activation leading to an increase in death receptor 5 (DR5) levels and a decrease in the antiapoptotic proteins survivin and bcl-2 levels.