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 microM 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.
Zhang
W
W
Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles 90033, USA.
Lawa
R E
RE
Hintona
D R
DR
Su
Y
Y
Couldwell
W T
WT
D000470:Alkaloids / Q000494:pharmacology; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009447:Neuroblastoma / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000873:Anthracenes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D013629:Tamoxifen; D010569:Perylene; C004965:hypericin; D011493:Protein Kinase C; D019311:Staurosporine