The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways.
Chelidonine is a tertiary benzophenanthridine alkaloid known to cause mitotic arrest and to interact weakly with tubulin. Our interest in chelidonine began when we found it to be a major contaminant of Ukrain, which is a compound reported to be selectively toxic to malignant cells. The effects of chelidonine in two normal (monkey kidney and Hs27), two transformed (Vero and Graham 293) and two malignant (WHCO5 and HeLa) cell lines, were examined. Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 microM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK).
Panzer
A
A
Department of Physiology, University of Pretoria, South Africa.
Joubert
A M
AM
Bianchi
P C
PC
Hamel
E
E
Seegers
J C
JC
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D006367:HeLa Cells; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D010617:Phenanthridines; D011108:Polymers; D015398:Signal Transduction / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism*; D014709:Vero Cells
D000470:Alkaloids; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D010617:Phenanthridines; D011108:Polymers; D014404:Tubulin; C062047:chelidonine; D016203:CDC2 Protein Kinase; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases