melatonin acts locally within the breast tumor in an antiaromatase-like fashion

Melatonin Blocks Breast Tumor Estrogen Synthesis in Rats

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NEW YORK (Reuters Health) Feb 08 - Melatonin may block the growth of endocrine-responsive breast cancer by preventing testosterone from aromatizing to estrogen in tumor tissue, according to murine studies by Spanish researchers.

Melatonin is thought to block growth of hormone-dependent breast tumors via two mechanisms: downregulation of steroid synthesis and selective estrogen receptor modulation, Dr. Emilio J. Sanchez-Barcelo of the University of Cantabria in Santander, and colleagues note in the January 15th issue of the International Journal of Cancer.

In earlier work, the team showed, in studies with MCF-7 human breast cancer cells, that melatonin at levels similar to human blood concentrations blocked estrogen biosynthesis locally by downregulating expression of aromatase.

To investigate the hormone's effects in vivo, they administered the hormone to ovariectomized rats with DMBA-induced mammary tumors. Some animals also were given testosterone. Ovary removal reduced tumor size while testosterone increased it, except when animals were also given melatonin or aminoglutethimide, an aromatase inhibitor.

Both castrated animals and those treated with melatonin were more likely to survive than animals that were not castrated. Aromatase activity also was lowest in tumors from animals that had been given melatonin, while incubating microsomal tumor fractions with melatonin reduced aromatase activity.

No increases in circulating estradiol were seen in rats given testosterone, the researchers note, indicating that the hormone's tumor-growth-promoting effects were exerted by estrogens formed locally. Production of estrogen within tumors, they add, is particularly important in the pathogenesis of hormone-dependent breast cancer in post-menopausal women.

Thus, the investigators conclude, the findings make "melatonin an interesting compound to be tested for its possible therapeutic value in breast cancer."

Int J Cancer 2006;274-278.