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Adrenoceptors: Non Conventional Target for Breast Cancer?

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Abstract:

Epinephrine and Norepinephrine, typically released during stress bind to nine different adrenoceptors (AR) which classically control the cardiovascular and respiratory systems. New targets were described for the many agonists and antagonists developed for these AR, as the central nervous system. During the last three decades, AR expression and action on the mammary gland/breast were extensively investigated. In the cow mammary gland, good milkability was associated with low density of β2-AR and high density of α2-AR. In the rat normal mammary gland, β-AR are expressed in the epithelial cells, alveoli, ducts, and adipocytes showing an exquisite regulation by steroid hormones and prolactin. In rat dimethylbenz(a)anthracene (DMBA) tumors, a close correlation was observed between tumor growth and β-AR concentration. β2-AR were described in numerous human cell lines and breast tumors. The action of β-adrenergic compounds on cell proliferation is contradictory. While some authors found that β-agonists significantly inhibit cancer cell proliferation and tumor growth in mice, others described a significant reduction in DNA synthesis by β-blockers. Also, positive effects of β-AR on human carcinoma cell migration have been described.

α2-AR are expressed in human breast cancer and non-cancer cell lines, their stimulation being associated with increased cell proliferation. In vivo clonidine increased tumor growth and α2-adrenergic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behaving as an inverse agonist. Therefore, the numerous adrenergic β- and α-AR agonists or antagonists could prove to be unexpected therapeutic options for mammary gland/ breast and mainly breast cancer.

Keywords: Beta-adrenoceptors; alpha-adrenoceptors; breast cancer; mammary tumor; normal breast

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709788186048

Affiliations: Instituto de Biologia y Medicina Experimental-CONICET, Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina.

Publication date: May 1, 2009

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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