Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics
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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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- Hayama Tadashi
- 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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Abstract
<p>Previously, we developed a method to evaluate states of cells treated with anticancer drugs via the comprehensive analysis of amino acids, termed amino acid metabolomics. In the present study, we evaluated the effects of the anticancer drugs, gemcitabine hydrochloride and pyrvinium pamoate, on the proliferation of a pancreatic cancer cell line (PANC-1) under hypoglycemic conditions using amino acid metabolomics. Intracellular and extracellular amino acid profiles of PANC-1 were determined by hydrophilic interaction chromatography-tandem mass spectrometry with simple pretreatment. Changes to the drugs’ anticancer effects resulting from glucose starvation conditions were presented in score plots obtained from principal component analyses. In particular, the analysis of intracellular amino acids was found to be the superior approach because the results allowed a clearer assessment of the cell state. Further, orthogonal partial least squares discriminant analysis was performed to search for amino acid candidates that discriminate with anticancer drug-treated PANC-1 cells. We identified several amino acids that might be able to distinguish the drug-treated group from the control group. These results might provide a better understanding of the mechanisms underlying cell responses such as drug resistance or austerity. The present study is the first to evaluate the efficacy of anticancer drugs under glucose starvation based on the analysis of the variation of extracellular and intracellular amino acid profiles in vitro.</p>
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 41 (2), 220-228, 2018
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679610995328
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- NII Article ID
- 130006329269
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 028787170
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- PubMed
- 29386482
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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