Phenoxazine derivatives induce caspase-independent cell death in human glioblastoma cell lines, A-172 and U-251 MG

Ken Shirato, Kazuhiko Imaizumi, Akihisa Abe, Akio Tomoda

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    The apoptotic effects of 2-amino-4,4α-dihydro-4α, 7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 2-amino-phenoxazine-3-one (Phx-3) on human glioblastoma cell lines, A-172 and U-251 MG were studied. These phenoxazines extensively decreased the viability of A-172 and U-251 MG cells (IC50 of Phx-1: 60 μM, in both lines; IC50 of Phx-3: 10 and 3 μM, for A-172 and U-251 cells, respectively). Phx-1 and Phx-3 increased the population of annexin V and PI double-positive cells in A-172 and U-251 MG cells, resulting in cell death at late stage apoptosis/necrosis. The activities of caspase-3/7 were greatly increased in A-172 and U-251 MG cells treated with Phx-1 or Phx-3. However, a pan-caspase inhibitor, z-VAD-fmk, failed to reverse the antiproliferative and apoptotic effects of Phx-1 and Phx-3 in both cell lines. In conclusion, Phx-1 and Phx-3 exert significant anti-cancer effects against human glioblastoma cell lines, A-172 and U-251 MG, mediated by the caspase-independent apoptotic cell death pathway.

    Original languageEnglish
    Pages (from-to)201-208
    Number of pages8
    JournalOncology Reports
    Volume17
    Issue number1
    Publication statusPublished - 2007 Jan

    Keywords

    • 2-Amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one
    • 2-Aminophenoxazine-3-one
    • Apoptosis
    • Caspase
    • Glioblastoma

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

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