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Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative
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| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Molecular Cancer Therapeutics, 4, 2005, 7, S. 1121-1127 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon |
|---|---|
| author |
Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon |
| spellingShingle |
Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon Molecular Cancer Therapeutics Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative Cancer Research Oncology |
| author_sort |
hara, keiichi |
| spelling |
Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-05-0067 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative Molecular Cancer Therapeutics |
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American Association for Cancer Research (AACR), 2005 |
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American Association for Cancer Research (AACR), 2005 |
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1535-7163 1538-8514 |
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| title |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_unstemmed |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_full |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_fullStr |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_full_unstemmed |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_short |
Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_sort |
synergistic enhancement of trail- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-05-0067 |
| publishDate |
2005 |
| physical |
1121-1127 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>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.</jats:p> |
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| author | Hara, Keiichi, Okamoto, Mayumi, Aki, Toshihiko, Yagita, Hideo, Tanaka, Hirotoshi, Mizukami, Yoichi, Nakamura, Hiroshi, Tomoda, Akio, Hamasaki, Naotaka, Kang, Dongchon |
| author_facet | Hara, Keiichi, Okamoto, Mayumi, Aki, Toshihiko, Yagita, Hideo, Tanaka, Hirotoshi, Mizukami, Yoichi, Nakamura, Hiroshi, Tomoda, Akio, Hamasaki, Naotaka, Kang, Dongchon, Hara, Keiichi, Okamoto, Mayumi, Aki, Toshihiko, Yagita, Hideo, Tanaka, Hirotoshi, Mizukami, Yoichi, Nakamura, Hiroshi, Tomoda, Akio, Hamasaki, Naotaka, Kang, Dongchon |
| author_sort | hara, keiichi |
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| description | <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> |
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| imprint_str_mv | American Association for Cancer Research (AACR), 2005 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Hara, Keiichi Okamoto, Mayumi Aki, Toshihiko Yagita, Hideo Tanaka, Hirotoshi Mizukami, Yoichi Nakamura, Hiroshi Tomoda, Akio Hamasaki, Naotaka Kang, Dongchon 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-05-0067 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative Molecular Cancer Therapeutics |
| spellingShingle | Hara, Keiichi, Okamoto, Mayumi, Aki, Toshihiko, Yagita, Hideo, Tanaka, Hirotoshi, Mizukami, Yoichi, Nakamura, Hiroshi, Tomoda, Akio, Hamasaki, Naotaka, Kang, Dongchon, Molecular Cancer Therapeutics, Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative, Cancer Research, Oncology |
| title | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_full | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_fullStr | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_full_unstemmed | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_short | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_sort | synergistic enhancement of trail- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| title_unstemmed | Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-05-0067 |