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

摘要

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.DeltaPsim:mitochondrial transmembrane potentialAc-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-7A6CCCP:carbonyl cyanide-m-chlorophenylhydrazoneDiOC6(3):3,3'-dihexyloxacarbocyanine iodideMTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromideGaudichaudione 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.DeltaPsim:mitochondrial transmembrane potentialAc-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-7A6CCCP:carbonyl cyanide-m-chlorophenylhydrazoneDiOC6(3):3,3'-dihexyloxacarbocyanine iodideMTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide