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Melatonin inhibits telomerase activity in the MCF‐7 tumor cell line both in vivo and in vitro
Author(s) -
LeonBlanco Mercedes M.,
Guerrero Juan M.,
Reiter Russel J.,
Calvo Juan R.,
Pozo David
Publication year - 2003
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2003.00077.x
Subject(s) - telomerase , melatonin , telomerase reverse transcriptase , in vivo , biology , cell culture , in vitro , telomere , messenger rna , microbiology and biotechnology , medicine , endocrinology , biochemistry , dna , genetics , gene
In this study for the first time the relationship between melatonin and telomerase activity was investigated. Melatonin exhibits oncostatic properties, but the actual mechanism of action by which the indole reduces tumor cell activity is not clear. Telomerase is an enzyme responsible of telomere elongation and is activated in most human cancers. In the current in vivo study, eight nude mice received a MCF‐7 xenograft and thereafter they were treated for 5 weeks with 0.1 mg/mL of melatonin in the drinking water. Melatonin treatment caused a significant reduction in the weight of tumors and reduced metastases when compared with the control group. As indicated by the Telomerase Repeats Amplification Protocol (TRAP) assay, a significant decrease in telomerase activity was observed in the group treated with melatonin. In related in vitro studies, cultured MCF‐7 cells were treated with three different concentrations of melatonin and a control without indole treatment. A significant dose‐dependent decrease in Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, mRNA expression was observed in the melatonin‐treated cells. We also observed a significant reduction in TR, the RNA telomerase subunit, mRNA expression at physiological concentrations of melatonin (1 n m ). Significant differences in TEP1, an associated telomerase protein, mRNA expression were also observed. In conclusion, melatonin influences telomerase both in vivo and in vitro, decreasing its activity in the tumors of nude mice and the mRNA expression of the TERT and TR subunits, essential factors for the proper function of the telomerase enzyme.