epidermal-growth-factor and psi-tectorigenin

Expression of epidermal growth factor (EGF) receptor is often increased in various human carcinomas. Therefore, inhibition of the EGF/EGF receptor-induced signaling pathway may help to suppress these carcinomas. In the presence of Ca2+, EGF induces elongation of A431 cells in approximately 30 min. The cell elongation was shown to be accompanied by a reorganization of actin filaments. These phenotypical changes were specifically inhibited by a tyrosine kinase inhibitor, erbstatin, and inhibitors of phosphatidylinositol (PI) turnover such as psi-tectorigenin and inostamycin. The amount of filamentous actin was increased by EGF, which was also inhibited by these compounds. Long-term treatment of A431 cells with EGF induced the disappearance of cytoskeleton and aggregation of the cells, which was again inhibited by the PI turnover inhibitors. Thus tyrosine kinase and phosphatidylinositol turnover inhibitors were shown to inhibit the signaling pathways of EGF-induced cytoskeletal organization of A431 cells.

Topics: Actins; Calcium; Carcinoma; Cell Aggregation; Cytoskeleton; Epidermal Growth Factor; Furans; Humans; Hydroquinones; Isoflavones; Microscopy, Phase-Contrast; Phosphatidylinositols; Protein-Tyrosine Kinases; Tumor Cells, Cultured

Topics: Epidermal Growth Factor; Isoflavones; Type C Phospholipases

Psi-tectorigenin, an isoflavonoid, was isolated from a culture filtrate of actinomycetes as an inhibitor of epidermal growth factor-induced phosphatidylinositol turnover in cultured A431 cells. It inhibited phosphatidylinositol turnover with an IC50 of about 1 microgram/ml; thus, its inhibitory activity was 6-times stronger than that of genistein or orobol. When added to cultured A431 cells psi-tectorigenin inhibited phosphatidylinositol turnover without inhibiting epidermal growth factor receptor tyrosine protein kinase. Thus, psi-tectorigenin is a specific inhibitor of phosphatidylinositol turnover and may be a useful tool for the functional analysis of phosphatidylinositol turnover.

Topics: Actinomycetales; Cell Line; Epidermal Growth Factor; ErbB Receptors; Flavonoids; Isoflavones; Phosphates; Phosphatidylinositols; Protein-Tyrosine Kinases