Inhibition of signal transduction in EGF-dependent epithelial cell lines

The epidermal growth factor (EGF) receptor plays a pivotal role in growth regulation of epidermal keratinocytes. Its expression and function can be markedly altered during malignant transformation in squamous cell carcinoma. The present study investigated the potential of growth inhibition by signal-transduction inhibitors in EGF-dependent epithelial cell lines in vitro. Benign HaCaT keratinocytes and malignant A431 cells were grown in vitro and exposed to various concentrations of a panel of eleven kinase and phosphodiesterase inhibitors. Cell growth was measured after 24 h and 48 h using fluorescence labeling with Hoechst 33342 and propidium iodide. Significant growth inhibition was achieved with all inhibitors when applied to HaCaT cells. The strongest growth inhibition was achieved with inhibitors H-7, A3 and diacylglycerol kinase inhibitors I and II. A431 cells were inhibited significantly by H-7, A3 and H-9. Selected signal-transduction inhibitors such as A3, H-7 and H-9 acting on intracellular kinases are capable of suppressing growth of EGF-dependent benign and malignant epithelial cell lines in vitro. They might be of future potential in the treatment of epithelial cancer but further studies are necessary.