Amino Acid Metabolomics Using LC-MS/MS: Assessment of Cancer-Cell Resistance in a Simulated Tumor Microenvironment
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- TOMITA Ryoko
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- TODOROKI Kenichiro
- Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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- MARUOKA Hiroshi
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- YOSHIDA Hideyuki
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- FUJIOKA Toshihiro
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- NAKASHIMA Manabu
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- YAMAGUCHI Masatoshi
- Faculty of Pharmaceutical Sciences, Fukuoka University
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- NOHTA Hitoshi
- Faculty of Pharmaceutical Sciences, Fukuoka University
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Description
We performed a comprehensive quantification of 20 amino acids in RPMI 1640 medium-cultured human colorectal adenocarcinoma cells to evaluate the efficacy of 5-fluorouracil treatment under hypoxic and hypoglycemic conditions, which mimic the tumor microenvironment. In this study, we developed a simple and comprehensive analytical method by using LC-MS/MS connected to the Intrada amino acid column, which eluted amino acids within 9 min. The present method covered a linearity range of 3.6 – 1818 μM, except for Gly (227 – 1818 μM), Ala, Asp, His (7.1 – 1818 μM each), and Trp (3.6 – 909 μM). The limits of detection were in the range of 0.02 – 38.0 pmol per injection in a standard solution. Amino acid concentration data were analyzed using principal-component analysis to represent samples on two-dimensional graphs. Linear discriminant analysis was used to classify samples on the score plots. Using this approach, the effect of 5-fluorouracil treatment could be successfully discriminated at high discrimination rates. Moreover, several amino acids were extracted from corresponding loading plots as candidate markers for distinguishing the effects of the 5-fluorouracil treatment or tumor microenvironmental conditions. These results suggest that our proposed method might be a useful tool for evaluating the efficacy of anticancer drugs in the tumor microenvironment.
Journal
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- Analytical Sciences
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Analytical Sciences 32 (8), 893-900, 2016
The Japan Society for Analytical Chemistry
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Details 詳細情報について
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- CRID
- 1390001204259636224
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- NII Article ID
- 130005256428
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- NII Book ID
- AA10500785
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- ISSN
- 13482246
- 09106340
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- NDL BIB ID
- 027552984
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- PubMed
- 27506717
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed