Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line.
We have investigated the ionophoretic and apoptotic properties of the daucane sesquiterpene ferutinin and three related compounds, ferutidin, 2-alpha-hydroxyferutidin and teferin, all isolated from various species of plants from the genus Ferula. Ferutinin induced a biphasic elevation of intracellular Ca2+ in the leukemia T-cell line, Jurkat. First, a rapid calcium peak was observed and inhibited by BAPTA-AM. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through L-type calcium channels and sensitive to inhibition by EGTA. Moreover, ferutinin-induced apoptosis in Jurkat cells, and this event was preceded, in a cyclosporine-A sensitive manner, by a loss of mitochondrial transmembrane potential (DeltaPsim) and by an increase in intracellular reactive oxygen species. Ferutinin-induced DNA fragmentation was mediated by a caspase-3-dependent pathway, and was initiated independently of any specific phase of the cell cycle. The evaluation of ferutinin analogs in calcium mobilization and apoptosis assays showed strict structure-activity relationships, with p-hydroxylation of the benzoyl moiety being requested for activity.[1]References
- Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line. Macho, A., Blanco-Molina, M., Spagliardi, P., Appendino, G., Bremner, P., Heinrich, M., Fiebich, B.L., Muñoz, E. Biochem. Pharmacol. (2004) [Pubmed]
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