GROWTH-INHIBITION AND APOPTOSIS IN HUMAN NEUROBLASTOMA SK-N-SH CELLS INDUCED BY HYPERICIN, A POTENT INHIBITOR OF PROTEIN-KINASE-C

The effect of hypericin, an antiviral agent and inhibitor of protein kinase C (PKC), on cell proliferation and programmed death was investigated in the human neuroblastoma cell line SK-N-SH. Hypericin induced significant growth inhibition in a dose-dependent manner demonstrated by a microculture tetrazolium (MTT) assay. DNA isolated from cells treated with hypericin at concentrations over 1 mu M exhibited a 'ladder' pattern of oligonucleosome-sized fragments characteristic of apoptosis. Similarly, treatment of the cells with the PKC inhibitors staurosporine, tamoxifen or phorbol ester PMA for 72 h also resulted in apoptosis, suggesting that hypericin may be triggering an apoptotic signal in neuroblastoma cells, which at least in part may be mediated by the inhibition of PKC.