Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line.

Abstract:

: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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Macho A,Blanco-Molina M,Spagliardi P,Appendino G,Bremner P,Heinrich M,Fiebich BL,Muñoz E

doi

10.1016/j.bcp.2004.05.016

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

875-83

issue

5

eissn

0006-2952

issn

1873-2968

pii

S0006295204003247

journal_volume

68

pub_type

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