Involvement of hydrogen peroxide in histamine-induced modulation of WM35 human malignant melanoma cell proliferation

Histamine is a recognized growth factor in melanoma, and exogenous histamine produces a dual effect on proliferation. We have previously reported that histamine at micromolar concentrations reduces the proliferation of melanoma cell lines. To investigate the mechanism by which histamine inhibits proliferation of WM35 human melanoma cells, we have studied the involvement of histamine in reactive oxygen species production and antioxidant enzyme regulation in these cells. Results indicate that histamine treatment (10 microM) significantly increased hydrogen peroxide levels, whereas it slightly decreased superoxide levels associated with an enhancement of superoxide dismutase and a reduction in catalase activity. Additionally, catalase treatment reversed the inhibitory effect of histamine on proliferation, and various treatments that reduce hydrogen peroxide formation increased proliferation of these cells. Furthermore, we demonstrate that the inhibition of proliferation produced by histamine was mediated at least in part by an induction of cell senescence. We conclude that hydrogen peroxide is involved in histamine-mediated modulation of proliferation in malignant melanoma cells.