Caspase-independent cell death revealed in human gastric cancer cell lines, MKN45 and KATO III treated with phenoxazine derivatives

Teruhiko Kasuga, Takafumi Tabuchi, Ken Shirato, Kazuhiko Imaizumi, Akio Tomoda

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    We examined whether phenoxazine derivatives such as 2-amino-4,4α- dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 2-aminophenoxazine-3-one (Phx-3) may have anticancer effects on the human gastric cancer cell lines, MKN45, MKN74, MKN7 and KATO III in vitro. Phx-1 inhibited the growth of these cancer cells in a dose- and time-dependent manner. The IC50 was approximately 65, 25, 100 and 70 μM for MKN45, MKN74, MKN7 and KATO III respectively, after 72 h. Phx-3 exerted stronger antiproliferative effects against these cancer cells (IC50: approximately 5, 1, 10 and 10 μM for MKN45, MKN74, MKN7 and KATO III, respectively, after 72 h) than Phx-1. Phx-1 and Phx-3 increased the population of TUNEL-positive cells in MKN45 and KATO III time-dependently from 24 to 72 h, suggesting that Phx-1 and Phx-3 have apoptotic activity against these gastric cancer cells. The activity of effector caspase-3 significantly increased in MKN45 treated with Phx-3 for 24 h, but did not altered in the cells treated with Phx-1 for 24 h. When z-VAD-fmk, a pan-caspase inhibitor, was co-treated for 24 h, Phx-3-stimulated caspase-3 activity in MKN45 was reversed to the levels of normal activity, while the antiproliferative and apoptotic effects of Phx-3 against the cells were maintained. The activity of caspase-3 was not activated in KATO III by 24 h exposure for Phx-1 or Phx-3. In conclusion, both phenoxazines prevent the growth of the human gastric cancer cell lines, MKN45 and KATO III in vitro, and cause the apoptosis of these cell lines via a caspase-independent pathway. Although the intracellular action mechanisms of Phx-1 and Phx-3 are still unclear, these phenoxazines may be useful for the treatment of gastric cancer in the future.

    Original languageEnglish
    Pages (from-to)409-415
    Number of pages7
    JournalOncology Reports
    Volume17
    Issue number2
    Publication statusPublished - 2007 Feb

    Fingerprint

    Caspases
    Stomach Neoplasms
    Cell Death
    Cell Line
    Caspase 3
    Inhibitory Concentration 50
    Effector Caspases
    Caspase Inhibitors
    In Situ Nick-End Labeling
    Growth
    phenoxazine
    Neoplasms
    Apoptosis
    Population

    Keywords

    • Caspase-independent apoptosis
    • Cell cycle arrest
    • Gastric cancer cells
    • Phenoxazines

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Caspase-independent cell death revealed in human gastric cancer cell lines, MKN45 and KATO III treated with phenoxazine derivatives. / Kasuga, Teruhiko; Tabuchi, Takafumi; Shirato, Ken; Imaizumi, Kazuhiko; Tomoda, Akio.

    In: Oncology Reports, Vol. 17, No. 2, 02.2007, p. 409-415.

    Research output: Contribution to journalArticle

    Kasuga, T, Tabuchi, T, Shirato, K, Imaizumi, K & Tomoda, A 2007, 'Caspase-independent cell death revealed in human gastric cancer cell lines, MKN45 and KATO III treated with phenoxazine derivatives', Oncology Reports, vol. 17, no. 2, pp. 409-415.
    Kasuga, Teruhiko ; Tabuchi, Takafumi ; Shirato, Ken ; Imaizumi, Kazuhiko ; Tomoda, Akio. / Caspase-independent cell death revealed in human gastric cancer cell lines, MKN45 and KATO III treated with phenoxazine derivatives. In: Oncology Reports. 2007 ; Vol. 17, No. 2. pp. 409-415.
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    AU - Shirato, Ken

    AU - Imaizumi, Kazuhiko

    AU - Tomoda, Akio

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