Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity
Article first published online: 3 AUG 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 118, Issue 2, pages 274–278, 15 January 2006
How to Cite
Cos, S., González, A., Güezmes, A., Mediavilla, M. D., Martínez-Campa, C., Alonso-González, C. and Sánchez-Barceló, E. J. (2006), Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. Int. J. Cancer, 118: 274–278. doi: 10.1002/ijc.21401
- Issue published online: 9 NOV 2005
- Article first published online: 3 AUG 2005
- Manuscript Accepted: 6 JUN 2005
- Manuscript Received: 4 APR 2005
- Spanish MCYT. Grant Number: BFI2003-06305
- Institute of Health “Carlos III”. Grant Number: PI042603.
- breast cancer;
Melatonin inhibits the growth of breast cancer cells by interacting with estrogen-responsive pathways, thus behaving as an antiestrogenic hormone. Recently, we described that melatonin reduces aromatase expression and activity in MCF-7 human breast cancer cells, thus modulating the local estrogen biosynthesis. To investigate the in vivo aromatase-inhibitory properties of melatonin in our current study, this indoleamine was administered to rats bearing DMBA-induced mammary tumors, ovariectomized (ovx) and treated with testosterone. In these castrated animals, the growth of the estrogen-sensitive mammary tumors depends on the local aromatization of testosterone to estrogens. Ovariectomy significantly reduced the size of the tumors while the administration of testosterone to ovx animals stimulated tumor growth, an effect that was suppressed by administration of melatonin or the aromatase inhibitor aminoglutethimide. Uterine weight of ovx rats, which depends on the local synthesis of estrogens, was increased by testosterone, except in those animals that were also treated with melatonin or aminoglutethimide. The growth-stimulatory effects of testosterone on the uterus and tumors depend exclusively on locally formed estrogens, since no changes in serum estradiol were appreciated in testosterone-treated rats. Tumors from animals treated with melatonin had lower microsomal aromatase activity than tumors of animals from other groups, and incubation with melatonin decreased the aromatase activity of microsomal fractions of tumors. Animals treated with melatonin had the same survival probability as the castrated animals and significantly higher survival probability than the uncastrated. We conclude that melatonin could exert its antitumoral effects on hormone-dependent mammary tumors by inhibiting the aromatase activity of the tumoral tissue. © 2005 Wiley-Liss, Inc.