Histamine Inhibits Cell Proliferation and Modulates the Expression of Bcl-2 Family Proteins via the H2 Receptor in Human Pancreatic Cancer Cells

GRACIELA CRICCO; GABRIELA MARTIN; VANINA MEDINA; MARIEL NÚÑEZ; NORA MOHAMAD; MÁXIMO CROCI; ERNESTO CRESCENTI; ROSA BERGOC; ELENA RIVERA

ANTICANCER RESEARCH

J.G. Delinassios Institute of anticancer Research

Lugar: Athens; Año: 2006 vol. 26 p. 4443 - 4450

0250-7005

  In this study, the mechanisms involved in the inhibitory effect of histamine (HA) on PANC-1 cell proliferation were investigated. The action of HA on cell growth was evaluated using the determination of the cell doubling time from experimental growth curves and cell cycle analysis using a flow cytometer. The expression of proteins related to cell death and proliferation (PCNA, p53, c-Fos and Bcl-2 family proteins) was studied using Western blot, immunocytochemistry and flow cytometric analysis. The results indicated that HA produced an accumulation of PANC-1 cells in G0/G1 phase and increased the doubling time via H2 histamine receptor (H2R) stimulation. Expression of p53, c- Fos and Bcl-2 were not modulated by HA. However, HA decreased PCNA and Bax expression, while it increased the Bcl-x level. In summary, the antiproliferative effect exerted by HA was associated with a G0/G1 phase arrest and a modulation of the Bcl-2 family proteins.