Cytotoxic effects of sinococuline

Three alkaloids, aknadinine, 1-nitroaknadinine and sinococuline, isolated from Stephania sutchuenensis were studied for their effects on a fibroblast cell line, eight tumour cell lines and a rat alveolar macrophage culture. Sinococuline is an effective tumour cell growth inhibitor whereas the toxicity of aknadinine and 1-nitroaknadinine towards all tested cells is low. A dose-dependent decrease in cell viability and in the uptake of tritiated-thymidine, -leucine and -uridine by these cells was observed when they were grown in the presence of sinococuline for 24 h. Exposure to sinococuline in vitro also altered the macrophage function by reducing the production of tumour necrosis factor and reactive nitrogen intermediates. Human leukaemic HL60 cells and mouse fibroblast L929 cells were used to study the underlying mechanism of cytotoxicity and apoptosis seems to be the mode of death induced by sinococuline.