Regulation of the expression of death receptors and their ligands by melatonin in haematological cancer cell lines and in leukaemia cells from patients
Sara Casado-Zapico
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorVanesa Martín
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorGuillermo García-Santos
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorJezabel Rodríguez-Blanco
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Search for more papers by this authorAna M. Sánchez-Sánchez
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorElisa Luño
Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorCarlos Suárez
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorJuana M. García-Pedrero
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorSofía T. Menendez
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorIsaac Antolín
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Search for more papers by this authorCarmen Rodriguez
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorSara Casado-Zapico
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorVanesa Martín
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorGuillermo García-Santos
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorJezabel Rodríguez-Blanco
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Search for more papers by this authorAna M. Sánchez-Sánchez
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorElisa Luño
Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorCarlos Suárez
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorJuana M. García-Pedrero
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorSofía T. Menendez
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
Search for more papers by this authorIsaac Antolín
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Search for more papers by this authorCarmen Rodriguez
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain
Search for more papers by this authorE-mail: [email protected].
Abstract
Abstract: Incorporation of new therapeutic agents remains as a major challenge for treatment of patients with malignant haematological disorders. Melatonin is an indolamine without relevant side effects. It has been shown previously to exhibit synergism with several chemotherapeutic drugs in Ewing sarcoma cells by potentiating the extrinsic pathway of apoptosis. It also sensitizes human glioma cells against TRAIL by increasing DR5 expression. Here, we report the induction of cell death by melatonin in several human malignant haematological cell lines through the activation of the extrinsic pathway of apoptosis. Such activation was mediated by the increase in the expression of the death receptors Fas, DR4 and DR5 and their ligands Fas L and TRAIL, with a remarkable rise in the expression of Fas and Fas L. The cytotoxic effect and the increase in Fas and Fas L were dependent on Akt activation. Results were corroborated in blasts from bone marrow and peripheral blood of acute myeloid leukaemia patients, where melatonin induced cell death and increased both Fas and Fas L expressions. We conclude that melatonin may be considered as a potential antileukaemic agent and its therapeutic use, either alone or in combination with current chemotherapeutic drugs, should be taken into consideration for further research.
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