Xanthoangelol, a major chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma and leukemia cells.
Xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, was evaluated for cell toxicity and apoptosis-inducing activity in human neuroblastoma (IMR-32) and leukemia (Jurkat) cells. Xanthoangelol concentration-dependently reduced the survival rates of both cell lines as revealed by the trypan blue exclusion test. Early apoptosis induced by 4 h incubation with xanthoangelol was detected using flow cytometry after double-staining with annexin V and propidium iodide (PI). Western blot analysis showed that xanthoangelol markedly reduced the level of precursor caspase-3 and increased the level of cleaved caspase-3, but Bax and Bcl-2 proteins were not affected. These results suggest that xanthoangelol induces apoptotic cell death by activatation of caspase-3 in neuroblastoma and leukemia cells through a mechanism that does not involve Bax/Bcl-2 signal transduction. Therefore, xanthoangelol may be applicable as an effective drug for treatment of neuroblastoma and leukemia.
Tabata
Keiichi
K
Clinical Pharmacy Center, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Motani
Kou
K
Takayanagi
Noriya
N
Nishimura
Reiko
R
Asami
Satoru
S
Kimura
Yumiko
Y
Ukiya
Motohiko
M
Hasegawa
Daisuke
D
Akihisa
Toshihiro
T
Suzuki
Takashi
T
D029969:Angelica / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002599:Chalcone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D002599:Chalcone; C068244:xanthoangelol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases