Journal
JOURNAL OF PINEAL RESEARCH
Volume 50, Issue 3, Pages 345-355Publisher
WILEY
DOI: 10.1111/j.1600-079X.2010.00850.x
Keywords
apoptosis; death receptors; extrinsic pathway; leukaemia; melatonin; patients
Categories
Funding
- MEC [SAF2007-64726]
- FIS [PI061803, FI07-00094]
- Instituto de Salud Carlos III (ISCIII) [RD06/0020/1042, RD06/0020/0034]
- FICYT [BP06-161, COF08-35, COF08-39, BP08-007]
- IUOPA
- University of Oviedo
- Minister of Science and Education (MEC)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available