Mitochondrial destabilisation and caspase-3 activation are involved in the apoptosis of Jurkat cells induced by gaudichaudione A, a cytotoxic xanthone.
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.
Wu
Xiaohua
X
Department of Pharmacology, Faculty of Medicine and Science, National University of Singapore, Singapore.
Cao
Shugeng
S
Goh
Sweehock
S
Hsu
Anne
A
Tan
Benny K H
BK
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D029760:Garcinia; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014966:Xanthenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044004:Xanthones
D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D010936:Plant Extracts; D014966:Xanthenes; D044004:Xanthones; C458581:gaudichaudione A; C009689:xanthone; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases