Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2

Seiko Kato, Ken Shirato, Kazuhiko Imaizumi, Hiroko Toyota, Junichiro Mizuguchi, Masato Odawara, Xiao Fang Che, Shinichi Akiyama, Akihisa Abe, Akio Tomoda

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    The aim of this study was to investigate the anticancer effects of the phenoxazine derivatives, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H- phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H- phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on human pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2, in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily of cytokines. Of these three phenoxazines, Phx-1 and Phx-3 inhibited proliferation of KLM-1 dose-dependently, but Phx-2 did not. Phx-3 caused both apoptosis and necrosis in KLM-1 cells, as evidenced by the phosphatidylserine externalization and propidium iodide permeable cells detected by a flow cytometric method using annexin-V and propidium iodide. Down-regulation of Bcl-2 expression appeared to be involved in the Phx-3-induced cell death. TRAIL did not affect proliferation of KLM-1, and the inhibitory effects of Phx-1 and Phx-3 on the KLM-1 cell line were not augmented by the combination with TRAIL. On the other hand, proliferation of the MIA-PaCa-2 cell line was not affected by Phx-1, Phx-2 and Phx-3, although it was significantly inhibited by TRAIL in a dose-dependent manner. Inhibitory effects of TRAIL on MIA-PaCa-2 were synergistically augmented by the addition of Phx-1 and Phx-3, but not by Phx-2. These results suggest that both Phx-1 and Phx-3 exert anticancer effects against human pancreatic cancer cells, KLM-1 and MIA-PaCa-2, through distinct action modes. Phx-1 and Phx-3 may be effective for the treatment of pancreatic cancer.

    Original languageEnglish
    Pages (from-to)843-848
    Number of pages6
    JournalOncology Reports
    Volume15
    Issue number4
    Publication statusPublished - 2006 Apr

    Fingerprint

    Pancreatic Neoplasms
    Tumor Necrosis Factor-alpha
    Apoptosis
    Ligands
    Cell Line
    Propidium
    Annexin A5
    Phosphatidylserines
    phenoxazine
    Cell Death
    Necrosis
    Down-Regulation
    Cytokines

    Keywords

    • Apoptosis
    • Pancreatic cancer cells
    • Phenoxazine
    • Proliferation inhibition
    • Tumor necrosis factor-related apoptosis-inducing ligand

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2. / Kato, Seiko; Shirato, Ken; Imaizumi, Kazuhiko; Toyota, Hiroko; Mizuguchi, Junichiro; Odawara, Masato; Che, Xiao Fang; Akiyama, Shinichi; Abe, Akihisa; Tomoda, Akio.

    In: Oncology Reports, Vol. 15, No. 4, 04.2006, p. 843-848.

    Research output: Contribution to journalArticle

    Kato, S, Shirato, K, Imaizumi, K, Toyota, H, Mizuguchi, J, Odawara, M, Che, XF, Akiyama, S, Abe, A & Tomoda, A 2006, 'Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2', Oncology Reports, vol. 15, no. 4, pp. 843-848.
    Kato, Seiko ; Shirato, Ken ; Imaizumi, Kazuhiko ; Toyota, Hiroko ; Mizuguchi, Junichiro ; Odawara, Masato ; Che, Xiao Fang ; Akiyama, Shinichi ; Abe, Akihisa ; Tomoda, Akio. / Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2. In: Oncology Reports. 2006 ; Vol. 15, No. 4. pp. 843-848.
    @article{ff8afc8b64dc41ceb18ff5dbe23da80c,
    title = "Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2",
    abstract = "The aim of this study was to investigate the anticancer effects of the phenoxazine derivatives, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H- phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H- phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on human pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2, in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily of cytokines. Of these three phenoxazines, Phx-1 and Phx-3 inhibited proliferation of KLM-1 dose-dependently, but Phx-2 did not. Phx-3 caused both apoptosis and necrosis in KLM-1 cells, as evidenced by the phosphatidylserine externalization and propidium iodide permeable cells detected by a flow cytometric method using annexin-V and propidium iodide. Down-regulation of Bcl-2 expression appeared to be involved in the Phx-3-induced cell death. TRAIL did not affect proliferation of KLM-1, and the inhibitory effects of Phx-1 and Phx-3 on the KLM-1 cell line were not augmented by the combination with TRAIL. On the other hand, proliferation of the MIA-PaCa-2 cell line was not affected by Phx-1, Phx-2 and Phx-3, although it was significantly inhibited by TRAIL in a dose-dependent manner. Inhibitory effects of TRAIL on MIA-PaCa-2 were synergistically augmented by the addition of Phx-1 and Phx-3, but not by Phx-2. These results suggest that both Phx-1 and Phx-3 exert anticancer effects against human pancreatic cancer cells, KLM-1 and MIA-PaCa-2, through distinct action modes. Phx-1 and Phx-3 may be effective for the treatment of pancreatic cancer.",
    keywords = "Apoptosis, Pancreatic cancer cells, Phenoxazine, Proliferation inhibition, Tumor necrosis factor-related apoptosis-inducing ligand",
    author = "Seiko Kato and Ken Shirato and Kazuhiko Imaizumi and Hiroko Toyota and Junichiro Mizuguchi and Masato Odawara and Che, {Xiao Fang} and Shinichi Akiyama and Akihisa Abe and Akio Tomoda",
    year = "2006",
    month = "4",
    language = "English",
    volume = "15",
    pages = "843--848",
    journal = "Oncology Reports",
    issn = "1021-335X",
    publisher = "Spandidos Publications",
    number = "4",

    }

    TY - JOUR

    T1 - Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2

    AU - Kato, Seiko

    AU - Shirato, Ken

    AU - Imaizumi, Kazuhiko

    AU - Toyota, Hiroko

    AU - Mizuguchi, Junichiro

    AU - Odawara, Masato

    AU - Che, Xiao Fang

    AU - Akiyama, Shinichi

    AU - Abe, Akihisa

    AU - Tomoda, Akio

    PY - 2006/4

    Y1 - 2006/4

    N2 - The aim of this study was to investigate the anticancer effects of the phenoxazine derivatives, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H- phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H- phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on human pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2, in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily of cytokines. Of these three phenoxazines, Phx-1 and Phx-3 inhibited proliferation of KLM-1 dose-dependently, but Phx-2 did not. Phx-3 caused both apoptosis and necrosis in KLM-1 cells, as evidenced by the phosphatidylserine externalization and propidium iodide permeable cells detected by a flow cytometric method using annexin-V and propidium iodide. Down-regulation of Bcl-2 expression appeared to be involved in the Phx-3-induced cell death. TRAIL did not affect proliferation of KLM-1, and the inhibitory effects of Phx-1 and Phx-3 on the KLM-1 cell line were not augmented by the combination with TRAIL. On the other hand, proliferation of the MIA-PaCa-2 cell line was not affected by Phx-1, Phx-2 and Phx-3, although it was significantly inhibited by TRAIL in a dose-dependent manner. Inhibitory effects of TRAIL on MIA-PaCa-2 were synergistically augmented by the addition of Phx-1 and Phx-3, but not by Phx-2. These results suggest that both Phx-1 and Phx-3 exert anticancer effects against human pancreatic cancer cells, KLM-1 and MIA-PaCa-2, through distinct action modes. Phx-1 and Phx-3 may be effective for the treatment of pancreatic cancer.

    AB - The aim of this study was to investigate the anticancer effects of the phenoxazine derivatives, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H- phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H- phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on human pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2, in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily of cytokines. Of these three phenoxazines, Phx-1 and Phx-3 inhibited proliferation of KLM-1 dose-dependently, but Phx-2 did not. Phx-3 caused both apoptosis and necrosis in KLM-1 cells, as evidenced by the phosphatidylserine externalization and propidium iodide permeable cells detected by a flow cytometric method using annexin-V and propidium iodide. Down-regulation of Bcl-2 expression appeared to be involved in the Phx-3-induced cell death. TRAIL did not affect proliferation of KLM-1, and the inhibitory effects of Phx-1 and Phx-3 on the KLM-1 cell line were not augmented by the combination with TRAIL. On the other hand, proliferation of the MIA-PaCa-2 cell line was not affected by Phx-1, Phx-2 and Phx-3, although it was significantly inhibited by TRAIL in a dose-dependent manner. Inhibitory effects of TRAIL on MIA-PaCa-2 were synergistically augmented by the addition of Phx-1 and Phx-3, but not by Phx-2. These results suggest that both Phx-1 and Phx-3 exert anticancer effects against human pancreatic cancer cells, KLM-1 and MIA-PaCa-2, through distinct action modes. Phx-1 and Phx-3 may be effective for the treatment of pancreatic cancer.

    KW - Apoptosis

    KW - Pancreatic cancer cells

    KW - Phenoxazine

    KW - Proliferation inhibition

    KW - Tumor necrosis factor-related apoptosis-inducing ligand

    UR - http://www.scopus.com/inward/record.url?scp=33746447990&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33746447990&partnerID=8YFLogxK

    M3 - Article

    C2 - 16525669

    AN - SCOPUS:33746447990

    VL - 15

    SP - 843

    EP - 848

    JO - Oncology Reports

    JF - Oncology Reports

    SN - 1021-335X

    IS - 4

    ER -