Histamine Modultes Proliferation In MCF-7 Human Breast Cancer Cell Line

MEDINA V; MASSARI N; CRICCO G; NUÑEZ M; CROCCI M; MARTIN G; BERGOC R; RIVERA E

Rosario, Argentina.

Congreso; XLII Reunión Anual de laSociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

We have reported that histamine (HA) regulates differentially signaling processes in normal and malignant mammary cells. The aim of the present study was to investigate the biological responses triggered by HA in breast cancer cells MCF-7 (ERa+). For this purpose we determined the expression of the HA receptors subtypes, H1R, H2R, H3R and H4R by RT-PCR; histidine decarboxylase (HDC) by western blot; intracellular polyamines by HPLC; HA content by immunostaining; cAMP production by RIA and cell proliferation by clonogenic assay. Results indicate that MCF-7 cells expressed the four HA receptors, HDC and presented a moderate level of intracellular HA. HA at 10 mM produced a 2-fold increase in cAMP levels and reduced cell proliferation (30%) and spermine levels (8,3±0,7 vs.10,6±0,4 pmol/µg protein). Similar effects were observed with lower HA doses. By using specific HA agonist and antagonist, we determined that HA decreased proliferation through the stimulation of the four HA receptors subtypes however, the most significant effect was exerted via H4R (70%). We conclude that the inhibitory effect of HA on proliferation is associated with an increase in cAMP levels that induces differentiation and a reduction of the intracellular spermine that is involved in cell growth. In addition, we observed that HA reduces the mitochondrial transmembrane potential suggesting a pro-apoptotic action. POSTER