EFFECTS OF ANTHRALIN AND HYPERICIN ON GROWTH-FACTOR SIGNALING AND CELL-PROLIFERATION IN-VITRO

The effect of the anthranoids, anthralin and hypericin, on epidermal g rowth factor receptor (EGF-R) activation and their degree of specifici ty was examined. Hypericin, but not anthralin, was found to inhibit bi nding of [I-125]-labelled epidermal growth factor (EGF) to HN5 squamou s carcinoma cells that overexpress EGFR. This effect was a result of a dose- and time-dependent reduction of EGF-R number and affinity. Neit her compound directly inhibited EGF-induced tyrosine phosphorylation o f the EGF-R in HN5 cells. Although anthralin and hypericin both inhibi ted the mitogenic effect of EGF in NR6/HER cells (IC(50)s = 100 nM and 10 mu M, respectively), they also had comparable effects on DNA synth esis in response to acidic fibroblast growth factor (aFGF) and platele t-derived growth factor (PDGF). When tested in proliferation assays us ing cells expressing differing numbers of EGF-R, the growth inhibitory effects of both compounds were independent of EGF-R number. We conclu de that, although anthralin and hypericin both inhibit EGF signalling, they do not act specifically on the EGF-R pathway. Moreover, their me chanisms of action do not appear to be comparable.