Histamine inhibits cell proliferation and modulates the expression of Bcl-2 family proteins via the H2 receptor in human pancreatic cancer cells.

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 by determining the cell doubling time from experimental growth curves and analysing the cell cycle 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 GO/Gl-phase and increased the doubling time via H2HA (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.