Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro

FEBS Letters

Akiyama, Kiyotaka¹  Nakagawa, Yoshihito²  Akao, Yukihiro³ 

[1] Pharmaceutical Frontiers Research Laboratories, Japan Tobacco, Inc., 6-2 Umegaoka, Yokohama 227-0052, Japan;The Second Department of Internal Medicine, Osaka Medical College, Daigaku-cho, Takatsuki, Osaka 569-8686, Japan;Gifu International Institute of Biotechnology, Mitake-cho, Kani-gun, Gifu 505-0116, Japan

关键词: Arsenic trioxide;    Neuroblastoma;    Apoptosis;    Caspase 3;    Glutathione;   

DOI  :  10.1016/S0014-5793(99)00841-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Arsenic trioxide (As₂O₃) induces clinical remission in acute promyelocytic leukemia, even in all-trans retinoic acid-refractory cases, with minimal toxicity at low (1–2 μM) concentration. We exposed various neuroblastoma cell lines to As₂O₃ at a concentration of 2 μM: as a result, seven of 10 neuroblastoma cell lines underwent apoptosis characterized by morphological changes and nucleosomal DNA fragmentation. As₂O₃-induced apoptosis in neuroblastoma cells was shown to occur through the activation of caspase 3, as judged from Western blot analysis and apoptosis inhibition assay. It seemed that the sensitivity of neuroblastoma cells to As₂O₃ was inversely proportional to their intracellular level of reduced glutathione. Taken together these results indicate that As₂O₃ would be a candidate as a therapeutic agent for treatment of neuroblastoma, which is a solid tumor, not only by systemic therapy but also by local therapy.

【 授权许可】

Unknown