Mitochondrial Destabilisation and Caspase-3 Activation are Involved in the Apoptosis of Jurkat Cells Induced by Gaudichaudione A, a Cytotoxic Xanthone

Abstract

Gaudichaudione A, a cytotoxic xanthone obtained from Garcinia gaudichaudii, displayed strong growth inhibitory effects against Jurkat human leukemic cells, parental murine leukemic P388 and P388/DOX-resistant cell lines, and exhibited similar cytotoxicity against P388/DOX as well as P388, but was less toxic toward normal human Chang liver cells. A variety of apoptotic events induced by gaudichaudione A at the mitochondrial and nuclear levels has been characterized. It appears that gaudichaudione A induced a collapse of the mitochondrial transmembrane potential. Caspase-3 was activated and induced internucleosomal DNA fragmentation and externalization of PS residues. The apoptotic features were also observed in ultrastructural studies.

Abbreviations

ΔΨ_m:mitochondrial transmembrane potential

Ac-DEVD-AMC:N-acetyl-Asp-Glu-Val-Asp-AMC
(7-amino-4-methylcoumarin)

Ac-DEVD-CHO:N-acetyl-Asp-Glu-Val-Asp-CHO (aldehyde)

Apo 2.7:anti-7A6

CCCP:carbonyl cyanide-m-chlorophenylhydrazone

DiOC₆(3):3,3′-dihexyloxacarbocyanine iodide

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-
trazolium bromide

Key words

Gaudichaudione A - flow cytometry - apoptosis - caspases - mitochondrial transmembrane potential - annexin V

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