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, Vanesa Martín, Guillermo García-Santos, Jezabel Rodríguez-Blanco, Ana M. Sánchez-Sánchez, Elisa Luño, Carlos Suárez, Juana M. García-Pedrero, Sofía T. Menendez, Isaac Antolín, Carmen Rodriguez

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)345-355
Number of pages11
JournalJournal of Pineal Research
Volume50
Issue number3
DOIs
StatePublished - Apr 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology

Keywords

  • Apoptosis
  • Death receptors
  • Extrinsic pathway
  • Leukaemia
  • Melatonin
  • Patients

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