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Biotransformation of melatonin in human breast cancer cell lines: role of sulfotransferase 1A1
Author(s) -
Aust Sylvia,
Jaeger Walter,
Klimpfinger Martin,
Mayer Klaus,
Baravalle Günther,
Ekmekcioglu Cem,
Thalhammer Theresia
Publication year - 2005
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 - 10.1111/j.1600-079x.2005.00246.x
Subject(s) - melatonin , biotransformation , sulfotransferase , cell culture , human breast , breast cancer , pineal gland , endocrinology , medicine , mammary gland , cancer , biology , chemistry , cancer research , biochemistry , sulfation , enzyme , genetics
The biologically active melatonin metabolite, 6‐hydroxymelatonin (6‐OHMel), is conjugated to form 6‐hydroxymelatonin sulfate (6‐OHMelS). To elucidate the role of the sulfotransferase (SULT) enzyme 1A1, considerably expressed in normal and malignant human breast cells, we measured the formation of 6‐OHMelS by ELISA in hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB231 (MDA) breast cancer cell lines after stable transfection with SULT1A1. In parent MDA cells, low SULT1A1 mRNA expression was associated with moderate 6‐OHMelS formation as determined after application (24 hr) of 0.1 μ m 6‐OHMel. As expected, overexpression of SULT1A1 in MDA cells resulted in a 2.9‐ and 110‐fold increase in 6‐OHMelS in the cytosol and cellular supernatant respectively. Furthermore, 6.3‐ and 115‐fold increases were observed after 0.5 μ m , and 12.6‐ and 101‐fold increases after 1 μ m 6‐OHMel respectively. In MCF‐7 cells, because of high basal SULT1A1 expression, only two‐ to threefold increases in 6‐OHMelS were observed after transfection with the enzyme. In total, 866 and 539 pmol/mg protein 6‐OHMelS were formed from 1 μ m 6‐OHMel in SULT1A1 overexpressing MDA and MCF‐7 cells, respectively, whereas application of 1 μ m melatonin produced only <1% of 6‐OHMelS. Possible interactions with the SULT1A1 substrate tamoxifen (tam), an anti‐estrogen applied in the therapy of breast cancer, were also studied. A concentration of 1 μ m tam increased 6‐OHMelS formation by approximately threefold in the presence of 1 μ m melatonin or 1 μ m 6‐OHMel respectively. However, no alterations were detected after application of 1 μ m 4‐hydroxy‐tamoxifen. In summary, we demonstrate the importance of SULT1A1 for the biotransformation of 6‐OHMel in human breast cancer cells. Our data further suggest that tam can modulate melatonin biotransformation.