Isobavachalcone, a Chalcone Constituent of Angelica keiskei, Induces Apoptosis in Neuroblastoma

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  • Nishimura Reiko
    Research Unit of Clinical Medicine, College of Pharmacy, Nihon University
  • Tabata Keiichi
    Research Unit of Clinical Medicine, College of Pharmacy, Nihon University
  • Arakawa Motoki
    Research Unit of Pharmacology, College of Pharmacy, Nihon University
  • Ito Yoshihisa
    Research Unit of Pharmacology, College of Pharmacy, Nihon University
  • Kimura Yumiko
    Research Unit of Analytical Chemistry of Pharmaceuticals, College of Pharmacy, Nihon University
  • Akihisa Toshihiro
    Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University
  • Nagai Hisashi
    Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University
  • Sakuma Atsuko
    Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University
  • Kohno Hideki
    Department of Applied Molecular Chemistry College of Industrial Technology, Nihon University
  • Suzuki Takashi
    Research Unit of Clinical Medicine, College of Pharmacy, Nihon University Department of Pediatrics and Child Health, Nihon University School of Medicine

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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.

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