Synergistic enhancement of TRAIL- and tumor necrosis factorα-induced cell death by a phenoxazine derivative

Keiichi Hara, Mayumi Okamoto, Toshihiko Aki, Hideo Yagita, Hirotoshi Tanaka, Yoichi Mizukami, Hiroshi Nakamura, Akio Tomoda, Naotaka Hamasaki, Dongchon Kang

研究成果: ジャーナルへの寄稿記事

21 引用 (Scopus)

抄録

2-Amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1) has been developed as a novel phenoxazine derivative having an anticancer activity on a variety of cancer cell lines as well as transplanted tumors in mice with minimal toxicity to normal cells. We examined the effects of Phx-1 on Jurkat cells, a human T cell line. Phx-1 inhibited proliferation of the cells in a dose-dependent manner but hardly induced cell death, suggesting that Phx-1 acts primarily as an antiproliferative reagent but not as a cytocidal drug. Phx-1 enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death about 100-fold. Tumor necrosis factor α, which alone does not induce cell death of Jurkat cells, caused apoptosis in combination with Phx-1. These enhancements of cell death were not due to up-regulation of the death receptors. Phx-1 decreased serum-induced phosphorylation of Akt, a kinase involved in cell proliferation and survival, and inhibited complex III of mitochondrial respiratory chain. Considering that both TRAIL and Phx-1 have only marginal cytotoxicity to most normal cells, Phx-1 may provide an ideal combination for cancer therapy with TRAIL.

元の言語英語
ページ(範囲)1121-1127
ページ数7
ジャーナルMolecular Cancer Therapeutics
4
発行部数7
DOI
出版物ステータス出版済み - 7 1 2005

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Cell Death
Tumor Necrosis Factor-alpha
Jurkat Cells
Cell Proliferation
Apoptosis
Cell Line
Neoplasms
Death Domain Receptors
Electron Transport Complex III
Electron Transport
Cell Survival
Phosphotransferases
Up-Regulation
Phosphorylation
Ligands
T-Lymphocytes
phenoxazine
Serum
Pharmaceutical Preparations
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Synergistic enhancement of TRAIL- and tumor necrosis factorα-induced cell death by a phenoxazine derivative. / Hara, Keiichi; Okamoto, Mayumi; Aki, Toshihiko; Yagita, Hideo; Tanaka, Hirotoshi; Mizukami, Yoichi; Nakamura, Hiroshi; Tomoda, Akio; Hamasaki, Naotaka; Kang, Dongchon.

:: Molecular Cancer Therapeutics, 巻 4, 番号 7, 01.07.2005, p. 1121-1127.

研究成果: ジャーナルへの寄稿記事

Hara, K, Okamoto, M, Aki, T, Yagita, H, Tanaka, H, Mizukami, Y, Nakamura, H, Tomoda, A, Hamasaki, N & Kang, D 2005, 'Synergistic enhancement of TRAIL- and tumor necrosis factorα-induced cell death by a phenoxazine derivative', Molecular Cancer Therapeutics, 巻. 4, 番号 7, pp. 1121-1127. https://doi.org/10.1158/1535-7163.MCT-05-0067
Hara, Keiichi ; Okamoto, Mayumi ; Aki, Toshihiko ; Yagita, Hideo ; Tanaka, Hirotoshi ; Mizukami, Yoichi ; Nakamura, Hiroshi ; Tomoda, Akio ; Hamasaki, Naotaka ; Kang, Dongchon. / Synergistic enhancement of TRAIL- and tumor necrosis factorα-induced cell death by a phenoxazine derivative. :: Molecular Cancer Therapeutics. 2005 ; 巻 4, 番号 7. pp. 1121-1127.
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