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.
Richter
A
A
CRC Medical Oncology Unit, Southampton General Hospital, U.K.
Davies
D E
DE
D000873:Anthracenes; D000875:Anthralin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D006133:Growth Substances; D010569:Perylene; C004965:hypericin; D004247:DNA; D066246:ErbB Receptors; D000875:Anthralin