Assessment of the Efficacy of Anticancer Drugs by Amino Acid Metabolomics Using Fluorescence Derivatization-HPLC

Tomita, Ryoko; Todoroki, Kenichiro; Machida, Kazuyuki; Nishida, Sho; Maruoka, Hiroshi; Yoshida, Hideyuki; Fujioka, Toshihiro; Nakashima, Mitsuyoshi; Yamaguchi, Masatoshi; Nohta, Hitoshi

doi:10.2116/analsci.30.751

Cited by 11 publications

(9 citation statements)

References 34 publications

(27 reference statements)

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“…11 HPLC is also used for metabolomics studies of various agents as well. 12 Nowadays, MS is a widely used technique for bioanalysis in which sample molecules get ionized and are separated based on their mass to charge ratio. Different ionization techniques employed in MS include electrospray ionization (ESI), chemical ionization, atmospheric pressure photoionization, atmospheric pressure chemical ionization (APCI), and matrix-assisted laser desorption ionization (MALDI).…”

Section: Modern Analytical Techniques For Bioanalysismentioning

confidence: 99%

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices

et al. 2019

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Significant numbers of newer anticancer drugs are regularly entering into the market worldwide to fight against different types of cancers. Analytical methodologies are being developed to quantitate those molecules in a variety of matrices during their drug development stages. Selection of biological matrices for developing bioanalytical methods is based on the mechanism of action, site of action, site of metabolism and route of excretion of the drugs or their metabolites. In this review, we have described the current scenario and advancements in bioanalytical techniques for quantification of different anticancer drugs in a variety of biomatrices with a special emphasis on sample preparation techniques. We have discussed and summarized different bioanalytical aspects for anticancer drugs, which can give direction to the researcher for choosing appropriate techniques for their quantification needs.

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Section: Modern Analytical Techniques For Bioanalysismentioning

confidence: 99%

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices

et al. 2019

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“…For statistical multivariate analysis, principal component analysis (PCA) and cluster analysis were performed as previously described. 15,16) Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to explore potential class-discrimination markers, and amino acids that mainly contributed to the classification were identified in S-plots generated using OPLS-DA.…”

Section: Measurement Of Extracellular and Intracellular Amino Acid Comentioning

confidence: 99%

“…Amino acid measurement was performed using fluorescence derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, followed by HPLC analysis. 15) The method is adequate to determine amino acid levels with high sensitivity and reproducibility. We could evaluate the efficacy of several anticancer drugs to colorectal adenocarcinoma cells (colo201) at the cultured cell level.…”

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confidence: 99%

Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics

Tomita

Todoroki

Hayama

et al. 2018

Biological & Pharmaceutical Bulletin

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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 drugtreated 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. Key words amino acid metabolomics; pancreatic cancer cell; glucose depletion; biomarker candidateMetabolomics is a comprehensive analysis of numerous small endogenous molecules contained in cells, biological fluids, and tissues. In addition to a complementary understanding of physiological functions, metabolomics is also a promising tool to explore potential biomarkers for diagnosis, prognosis, and therapeutic response.1) It has proven to be very useful not only in medical and life sciences, but also in clinical research, 2,3) drug discovery, 4) environmental toxicology, 5) and food science. 6,7) Recently, among the available focused metabolomics approaches, amino acid metabolomics analysis, which focuses on amino acids as key metabolites, such as aminoindex 8,9) or chiral amino acid metabolomics, 10-12) has received considerable attention because of its utility in the diagnosis and monitoring of pathological conditions. Exogenous and endogenous amino acids are hub substances in regulated metabolic networks, and are also relatively abundant in many biological samples. Therefore, they are thought to have superior properties as targets of focused metabolomics. In several studies, alterations in the free amino acid profile were found to be related to various disease states, such as cancer. 13,14) Previously, we evaluated the effect of several anticancer agents on cancer cell proliferation using amino acid metabolomics analysis of the culture medium. Amino acid measurement was performed using fluorescence der...

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“…10 Recently, we evaluated the effects of various anticancer drugs on cell growth using an amino acid metabolomics assessment of the cell culture medium. 11 The purpose of this previous study was to determine the therapeutic efficacy of anticancer drugs based on the changes in amino acid metabolism at the cellular level. Differences in the relative amino acid compositions of cells treated with three different anticancer drugs (5-fluorouracil , irinotecan hydrochloride, and cisplatin) were visualized through principal-component analysis (PCA) and partial leastsquares multivariate statistical analyses.…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Metabolomics Using LC-MS/MS: Assessment of Cancer-Cell Resistance in a Simulated Tumor Microenvironment

et al. 2016

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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.

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Assessment of the Efficacy of Anticancer Drugs by Amino Acid Metabolomics Using Fluorescence Derivatization-HPLC

Cited by 11 publications

References 34 publications

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices

Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics

Amino Acid Metabolomics Using LC-MS/MS: Assessment of Cancer-Cell Resistance in a Simulated Tumor Microenvironment

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