Adrenoceptors: Non Conventional Target for Breast Cancer?

LUTHY IA; BRUZZONE A; PÉREZ C; CASTILLO LF; CHIESSA JI; VÁZQUEZ SM; SARAPPA MG

CURRENT MEDICINAL CHEMISTRY.

Bentham Science Publishers

Año: 2009 vol. 2009 p. 1850 - 1862

0929-8673

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 was extensively investigated. In the cow mammary gland, good mil­ka­bility was asso­cia­ted with low density of beta2-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 beta-AR. Beta2_AR were described in nume­rous human cell lines and breast tumors. The action of beta-adrenergic compounds on cell proliferation is contradictory. While some authors found that beta-agonists sig­nificantly inhibit cancer cell proliferation and tumor growth in mice, others des­cribed a sig­nificant re­duc­­tion in DNA syn­thesis by beta-blockers. Also, positive effects of beta-AR on hu­man carcinoma cell migration have been described. Alpha2-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 alpha2-adre­ner­gic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behav­ing as an inverse agonist. Therefore, the numerous adre­nergic beta and alpha-AR ago­nists or antagonists could prove to be unexpected therapeutic options for mam­mary gland/ breast and mainly breast cancer.