Richter A, Davies D E
CRC Medical Oncology Unit, Southampton General Hospital, U.K.
Biochem Pharmacol. 1995 Dec 22;50(12):2039-45. doi: 10.1016/0006-2952(95)02106-x.
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.
研究了蒽类化合物、地蒽酚和金丝桃素对表皮生长因子受体（EGF-R）激活的影响及其特异性程度。发现金丝桃素而非地蒽酚能抑制[125I]标记的表皮生长因子（EGF）与过表达EGF-R的HN5鳞状癌细胞的结合。这种效应是EGF-R数量和亲和力呈剂量和时间依赖性降低的结果。两种化合物均未直接抑制HN5细胞中EGF诱导的EGF-R酪氨酸磷酸化。虽然地蒽酚和金丝桃素均抑制NR6/HER细胞中EGF的促有丝分裂作用（IC50分别为100 nM和10 μM），但它们对酸性成纤维细胞生长因子（aFGF）和血小板衍生生长因子（PDGF）刺激的DNA合成也有类似作用。当在使用表达不同数量EGF-R的细胞进行的增殖试验中进行测试时，两种化合物的生长抑制作用均与EGF-R数量无关。我们得出结论，虽然地蒽酚和金丝桃素均抑制EGF信号传导，但它们并非特异性作用于EGF-R途径。此外，它们的作用机制似乎并不相同。
