Inhibitory Effect of Cyclosporin A Peptide on Rat Hepatocytes Proliferation Induced by Mitogens

Rodriguez-Henche N., I. D. Román, J. Fueyo, C. Menor, J. A. Zueco, J. C. Prieto and L. G. Guijarro. Inhibitory effect of cyclosporin A peptide on rat hepatocytes proliferation induced by mitogens. Peptides 19(3) 427–435, 1998.—Treatment of cultured rat hepatocytes with cyclosporin A (0.01–1 μM) for 24, 48, or 72 h in the presence of insulin and epidermal growth factor induced an inhibition on cell proliferation in a time- and concentration-dependent manner, with an IC 50 = 0.05 μM CsA corresponding to 48-h treatment. The inhibitory effect of CsA at ≤0.1 μM doses for 48 h on [ 3H]thymidine uptake was reversed after withdrawal of the drug and subsequent addition of insulin plus EGF or serum; however, at 1 μM CsA the effect was irreversible and numerous bright small vesicles were observed. The molecular mechanism involved in CsA action in hepatocytes seems to be independent on cAMP and pertussis-toxin sensitive G proteins.