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Published on: January 15, 2016
Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death
Vanesa Martín1, Guillermo García-Santos, Jezabel Rodriguez-Blanco
1Departamento de Morfología y Biología Celular, Spain. martinvanesa@uniovi.es
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.
Insights
Melatonin enhances cancer therapy by increasing glioma cell sensitivity to TRAIL-induced apoptosis. This involves modulating protein activity, boosting death receptor 5 (DR5), and reducing anti-apoptotic proteins like survivin and bcl-2.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gliomas are often resistant to cancer-killing ligands like TRAIL.
- Melatonin exhibits known anti-tumor effects and can enhance chemotherapy.
- Understanding resistance mechanisms to TRAIL is crucial for developing effective glioma treatments.
Purpose of the Study:
- To investigate if melatonin can sensitize human glioma cells to TRAIL-induced apoptosis.
- To elucidate the molecular mechanisms underlying melatonin's potential sensitizing effects.
Main Methods:
- Treatment of A172 and U87 human glioma cells with melatonin and TRAIL.
- Assessment of cell apoptosis.
- Analysis of protein kinase C (PKC) activity.
- Evaluation of Akt activation.
- Measurement of death receptor 5 (DR5), survivin, and bcl-2 protein levels.
Main Results:
- Melatonin significantly increased TRAIL-induced apoptosis in A172 and U87 glioma cells.
- Melatonin modulated protein kinase C (PKC) activity.
- This modulation led to decreased Akt activation.
- DR5 levels were elevated, while anti-apoptotic proteins survivin and bcl-2 were decreased.
Conclusions:
- Melatonin enhances sensitivity of human glioma cells to TRAIL-induced apoptosis.
- The mechanism involves PKC modulation, reduced Akt activation, increased DR5, and decreased survivin/bcl-2.
- Melatonin represents a potential therapeutic agent to overcome TRAIL resistance in gliomas.
