Potentiation by a biscoclaurine alkaloid, cepharanthine, of the toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin in HeLa cells.

Cepharanthine, a biscoclaurine alkaloid, causes an 8-fold enhancement of the cytotoxic effect of a conjugate of epidermal growth factor (EGF) coupled with Pseudomonas exotoxin in HeLa cells. Cepharanthine also potentiates the effect of Pseudomonas exotoxin. Cepharanthine does not affect the binding and uptake of 125I-EGF by HeLa cells, but it delays the release of radioactivity associated with 125I-EGF into the medium. Analysis by colloidal silica gradients using cell homogenates suggests that 125I-EGF accumulates in the lysosomes of cells treated with cepharanthine and that [3H]cepharanthine accumulates in lysosomes. The pH in HeLa cell lysosomes is 5.2, and cepharanthine does not significantly increase the pH. Electron microscopy shows an increased number of electron-dense bodies and dilated Golgi apparatus after cepharanthine treatment. Cepharanthine appears to accumulate in lysosomes, and it may delay degradation of EGF-Pseudomonas exotoxin in the cells as does 125I-EGF.