Effects of anthralin and hypericin on growth factor signalling and cell proliferation in vitro.

The effect of the anthranoids, anthralin and hypericin, on epidermal growth factor receptor (EGF-R) activation and their degree of specificity was examined. Hypericin, but not anthralin, was found to inhibit binding of [125I]-labelled epidermal growth factor (EGF) to HN5 squamous carcinoma cells that overexpress EGF-R. This effect was a result of dose- and time-dependent reduction of EGF-R number and affinity. Neither compound directly inhibited EGF-induced tyrosine phosphorylation of the EGF-R in HN5 cells. Although anthralin and hypericin both inhibited the mitogenic effect of EGF in NR6/HER cells (IC50S = 100 nM and 10 microM, respectively), they also had comparable effects on DNA synthesis in response to acidic fibroblast growth factor (aFGF) and platelet-derived growth factor (PDGF). When tested in proliferation assays using cells expressing differing numbers of EGF-R, the growth inhibitory effects of both compounds were independent of EGF-R number. We conclude that, although anthralin and hypericin both inhibit EGF signalling, they do not act specifically on the EGF-R pathway. Moreover, their mechanisms of action do not appear to be comparable.