The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways

Chelidonine is a tertiary benzophenanthridine alkaloid known to cause mitot ic arrest and to interact weakly with tubulin. Our interest in chelidonine began when we found it to be a major contaminant of Ukrain(TM), which is a compound reported to be selectively toxic to malignant tells. The effects o f chelidonine in two normal (monkey kidney and Hs27), two transformed (Vero and Graham 293) and two malignant (WHCO5 and HeLa) cell lines, were examin ed. Chelidonine proved to be a weak inhibitor of cell growth, but no eviden ce for selective cytotoxicity was found in this study. It was confirmed tha t chelidonine inhibits tubulin polymerisation (IC50 = 24 muM), explaining i ts ability to disrupt microtubular structure in cells. A G2/M arrest result s, which is characterised by abnormal metaphase morphology, increased level s of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell line s examined to chelidonine leads to activation of the stress-activated prote in kinase/jun kinase pathway (SAPK/JNK).