Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma.
Six chalcones from Angelica keiskei KOIDZUMI (Ashitaba in Japanese) and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10(-4) M) exposure. Typical morphologic features of apoptosis, including cell shrinkage, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies, were observed in isobavachalcone-treated cells by Hoechst 33342 staining. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application. These results suggest that isobavachalcone induces apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells. Therefore, isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma.
Nishimura
Reiko
R
Research Unit of Clinical Medicine, College of Pharmacy, Nihon University, Funabashi, Chiba, Japan.
Tabata
Keiichi
K
Arakawa
Motoki
M
Ito
Yoshihisa
Y
Kimura
Yumiko
Y
Akihisa
Toshihiro
T
Nagai
Hisashi
H
Sakuma
Atsuko
A
Kohno
Hideki
H
Suzuki
Takashi
T
D029969:Angelica / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D047188:Chalcones / Q000302:isolation & purification / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D001562:Benzimidazoles; D061945:Caspase Inhibitors; D047188:Chalcones; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C468754:isobavachalcone; D020169:Caspases; C022616:thiazolyl blue; C017807:bisbenzimide ethoxide trihydrochloride