Melatonin enhances the inhibitory effect of aminoglutethimide on aromatase activity in MCF-7 human breast cancer cells.
The inhibition of the aromatase-induced intratumoral estrogen synthesis is one of the main anticancer pharmacological strategies. The aim of this paper was to study if a melatonin pretreatment prior to aminoglutethimide increases the efficiency of the aromatase inhibitor used in treating breast cancer. Aminoglutethimide (100 microM) and melatonin (1 nM) significantly decreased cellular aromatase activity in unpretreated MCF-7 cells. A sequential regimen of melatonin (1 nM) followed 24 h later by aminoglutethimide (100 microM) induced a significantly higher decrease in MCF-7 cell aromatase activity to below the values obtained in unpretreated cells. Melatonin treatment inhibited aromatase mRNA expression in unpretreated cells and a sequential treatment of cells with melatonin followed by aminoglutethimide induced a significant inhibition in the aromatase mRNA expression as compared to cells exposed to the same doses of aminoglutethimide, but without melatonin pretreatment. The present study demonstrates that a treatment with melatonin followed by aminoglutethimide is the most effective way of reducing the aromatase activity in the MCF-7 cell line. The aminoglutethimide inhibitory effect is more potent when MCF-7 cells are pre-exposed to melatonin. Our results suggest that melatonin pretreatment increases the reduction of the aromatase activity of cells exposed to aminoglutethimide as a result of the decrease in the aromatase mRNA expression. The findings presented here point to melatonin pretreatment as a novel and interesting means to increase the efficacy of competitive aromatase inhibitors used in treating breast cancer.
Martínez-Campa
Carlos
C
Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain.
González
Alicia
A
Mediavilla
Maria Dolores
MD
Alonso-González
Carolina
C
Sánchez-Barceló
Emilio J
EJ
Cos
Samuel
S
D000616:Aminoglutethimide / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001141:Aromatase / Q000096:biosynthesis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; D012333:RNA, Messenger; D000616:Aminoglutethimide; D001141:Aromatase; D008550:Melatonin