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Tumor-specificity a...
Tumor-specificity and type of cell death induced by phenoxazines
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Suzuki, F. (author)
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Hashimoto, K. (author)
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Ishihara, M. (author)
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- Westman, Gunnar, 1964 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Samuelsson, Kristin, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry,University of Gothenburg
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Kawase, M., 0 (author)
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Motohashi, N., 0 (author)
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Sakagami, H. (author)
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:6B, s. 4233-4238
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Abstract
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- Phenoxazines have shown diverse biological activities, but tumor-specific cytotoxic activity has not been investigated. A total of 24 phenoxazine derivatives (WM1-24) was investigated for their relative cytotoxicity against human tumor cell lines vs. normal cells. WM7 and WM8 showed the highest tumor-specificity index of 4.3 and 4.8, respectively. Considerable difference in drug-sensitivity was found among these tumor cell lines. Human promyelocytic leukemia HL-60 cells showed the highest sensitivity to both WM7 and WM8, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), and human gingival fibroblast (HGF), pulp cell (HPC) and periodontal ligament fibroblast (HPLF) were the most resistant. WM7 and WM8 induced little or no internucleosomal DNA fragmentation, and activated caspase-3 in HSC-2, HSC-4 and human glioblastoma T98G cells. These compounds failed to induce autophagic cell death, as judged by acridine orange and microtubule-associated protein I light chain 3 (LC3)-GFP assays. These results suggested that the higher cytotoxicity of WM7 and WM8 are derived from the positively-charged quaternary nitrogen substituents on the phenoxazine ring and the electron density of nitrogen at N12, and that inhibition of autophagy is not always coupled with apoplosis induction.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Kemiteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Chemical Engineering (hsv//eng)
Keyword
- phenoxazines
- cytotoxicity
- cell death
- caspase
- type of cell death
- INDUCED APOPTOSIS
- INHIBITORS
- KETONES
- POTENT
- LINES
- KETONES
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Suzuki, F.
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Hashimoto, K.
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Ishihara, M.
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Westman, Gunnar, ...
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Samuelsson, Kris ...
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Kawase, M., 0
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show more...
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Motohashi, N., 0
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Sakagami, H.
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show less...
- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Chemical Enginee ...
- Articles in the publication
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Anticancer Resea ...
- By the university
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University of Gothenburg
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Chalmers University of Technology