With the aim of trying to discern the contribution of a direct action of the compounds on tumour cells, we performed in vitro studies to evaluate the effect of H4R agonists on the proliferative and apoptotic responses of 4T1 cells, which are known to express H4R at the mRNA and protein levels.23 The results demonstrated that histamine regulated the clonogenic proliferation of 4T1 cells in a dose-dependent manner, exhibiting an IC50 of 0.99 μmol L−1 (Fig. 5a). Here, HRH4 is linked to neoplasm.