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.
Cricco
Graciela
G
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Martín
Gabriela
G
Medina
Vanina
V
Núñez
Mariel
M
Mohamad
Nora
N
Croci
Máximo
M
Crescenti
Ernesto
E
Bergoc
Rosa
R
Rivera
Elena
E
D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D011970:Receptors, Histamine H2; D006632:Histamine