Biol. Pharm. Bull., 28(8),1404-1407, August 2005

Regular Articles

Xanthoangelol, a Major Chalcone Constituent of Angelica keiskei, Induces Apoptosis in Neuroblastoma and Leukemia Cells

Keiichi TABATA,^a Kou MOTANI,^a Noriya TAKAYANAGI,^a Reiko NISHIMURA,^a Satoru ASAMI,^a Yumiko KIMURA,^b Motohiko UKIYA,^c Daisuke HASEGAWA,^c Toshihiro AKIHISA,^c and Takashi SUZUKI^*,a,d

^a Clinical Pharmacy; ^b Chemical Analysis Center, College of Pharmacy, Nihon University; 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan: ^c Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University; 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8301, Japan: and ^d Department of Pediatrics, School of Medicine, Nihon University; 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-0032, Japan. * To whom correspondence should be addressed. e-mail: suzuki@pha.nihon-u.ac.jp

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.

Key words xanthoangelol; apoptosis; neuroblastoma; leukemia