Effect of histamine and the H2antagonist cimetidine on the growth and migration of human neoplastic gila

Abstract

Histamine is known to act, at least in part, as a growth factor, as production of this neurotransmitter has been found to accelerate the rate of tissue proliferation in wound repair, embryogenesis and malignant growth. Histamine favours in vivo tumour cell proliferation via H2 receptors. Cimetidine is an H2 blocker and has been shown to inhibit tumour cell growth. In the present study, the growth modulating effects of histamine and cimetidine were assessed on five cell lines derived from human brain tumours of different histological types and grades of malignancy. Each cell line was treated with either cimetidine or histamine for 24 h before kinetic analyses, with PCNA, or motility assays, using Transwell migration chambers incorporating a microporous membrane, were carried out. Cimetidine significantly inhibited cell proliferation in three out of the five cell lines, which may indicate the dependence of proliferation of these cell lines on stimulation of the H2 receptor. With regard to migration, it was observed that in the majority of cell lines, cimetidine induced migration whilst histamine inhibited it. It was concluded that the link between effects of histamine on proliferation and its effects on migration must be clarified using a larger sample of cell lines.