Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O′-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic 1H-NMR Study

Castro, Federica De; Benedetti, Michele; Antonaci, Giovanna; Coco, Laura Del; Pascali, Sandra Angelica De; Muscella, Antonella; Marsigliante, Santo; Fanizzi, Francesco Paolo

doi:10.3390/molecules23092301

Cited by 28 publications

(42 citation statements)

References 78 publications

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“…Indeed, it is reported to be associated with chemoresistance to platinum salts, which is one of the main treatments for ovarian cancer [10]. Myo-inositol and phosphocholine (ChoP) have been reported in SKOV3 cells and their cellular concentrations reduced after treatment of Ptac2S, a novel anticancer agent [11]. Glutamate was found to be higher in SKOV3 and RCC cells compared with other cell lines.…”

Section: Discussionmentioning

confidence: 99%

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Liu

Zhao

et al. 2020

Bioscience Reports

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Cancer cell lines are often used for cancer research. However, continuous genetic instability-induced heterogeneity of cell lines can hinder the reproducibility of cancer research. Molecular profiling approaches including transcriptomics, chromatin modification profiling, and proteomics are used to evaluate the phenotypic characteristics of cell lines. However, these do not reflect the metabolic function at the molecular level. Metabolic phenotyping is a powerful tool to profile the biochemical composition of cell lines. In the present study, 1H-NMR spectroscopy-based metabolic phenotyping was used to detect metabolic differences among five cancer cell lines, namely, lung (A549), colonic (Caco2), brain (H4), renal (RCC), and ovarian (SKOV3) cancer cells. The concentrations of choline, creatine, lactate, alanine, fumarate and succinate varied remarkably among different cell types. The significantly higher intracellular concentrations of glutathione, myo-inositol, and phosphocholine were found in the SKOV3 cell line relative to other cell lines. The concentration of glutamate was higher in both SKOV3 and RCC cells compared with other cell lines. For cell culture media analysis, isopropanol was found to be the highest in RCC media, followed by A549 and SKOV3 media, while acetone was the highest in A549, followed by RCC and SKOV3. These results demonstrated that 1H-NMR-based metabolic phenotyping approach allows us to characterize specific metabolic signatures of cancer cell lines and provides phenotypical information of cellular metabolism.

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Section: Discussionmentioning

confidence: 99%

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Liu

Zhao

et al. 2020

Bioscience Reports

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“…For a better understanding of metabolic pathways which can have a significant impact on a given biological process after C8 or C10 addition to U87MG cells, we performed two types of pathway analyses. Metabolite Set Enrichment Analysis, performed using the Small Molecule Pathway Database and Metabolic Pathway Analysis, performed using the KEGG database, which also calculates the impact of each pathway using topology analysis in addition to the classic Enrichment Analysis (Girelli et al, 2016;De Castro et al, 2018). According to both p-value and impact value, the analysis showed target pathways that could be potentially altered following C8 or C10 addition to U87MG cells.…”

Section: Metabolic Pathway and Metabolite Set Enrichment Analysesmentioning

confidence: 99%

Decanoic Acid and Not Octanoic Acid Stimulates Fatty Acid Synthesis in U87MG Glioblastoma Cells: A Metabolomics Study

et al. 2020

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Medium-chain fatty acids (MCFA) are dietary components with a chain length ranging from 6 to 12 carbon atoms. MCFA can cross the blood-brain barrier and in the brain can be oxidized through mitochondrial β-oxidation. As components of ketogenic diets, MCFA have demonstrated beneficial effects on different brain diseases, such as traumatic brain injury, Alzheimer's disease, drug-resistant epilepsy, diabetes, and cancer. Despite the interest in MCFA effects, not much information is available about MCFA metabolism in the brain. In this study, with a gas chromatographymass spectrometry (GC-MS)-based metabolomics approach, coupled with multivariate data analyses, we followed the metabolic changes of U87MG glioblastoma cells after the addition of octanoic (C8), or decanoic (C10) acids for 24 h. Our analysis highlighted significant differences in the metabolism of U87MG cells after the addition of C8 or C10 and identified several metabolites whose amount changed between the two groups of treated cells. Overall, metabolic pathway analyses suggested the citric acid cycle, Warburg effect, glutamine/glutamate metabolism, and ketone body metabolism as pathways influenced by C8 or C10 addition to U87MG cells. Our data demonstrated that, while C8 affected mitochondrial metabolism resulting in increased ketone body production, C10 mainly influenced cytosolic pathways by stimulating fatty acid synthesis. Moreover, glutamine might be the main substrate to support fatty acids synthesis in C10-treated cells. In conclusion, we identified a metabolic signature associated with C8 or C10 addition to U87MG cells that can be used to decipher metabolic responses of glioblastoma cells to MCFA treatment.

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“…For example, De Castro et al [ 145 ] studied Ptac2S and its related cytotoxicity to the cisplatin-resistant epithelial ovarian carcinoma (EOC), Skov-3 cells. In the study, they used NMR spectroscopy and multi-variate statistical analysis to observe how Skov-3 cells reacted to treatment with Ptac2S.…”

Section: An Introduction To Nmr Spectroscopymentioning

confidence: 99%

“…The authors also noticed an unexpected difference in lipid metabolite expression levels between the cells treated with Ptac2S and those treated with cisplatin. These results provide a possible explanation for how Ptac2S is able to overcome cisplatin resistance in Skov-3 cells [ 145 ].…”

Section: An Introduction To Nmr Spectroscopymentioning

confidence: 99%

“…The HMBC technique, while similar to HSQC, is an example of a heteronuclear 2D experiment that reveals correlations between nuclei separated by two or more chemical bonds while also suppressing one-bond correlations at the same time. This experiment combined with HSQC is often used to assign NMR spectra for studied molecules in drug design experiments [ 65 , 66 , 137 , 145 ].…”

Section: An Introduction To Nmr Spectroscopymentioning

confidence: 99%

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NMR as a “Gold Standard” Method in Drug Design and Discovery

et al. 2020

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Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.

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Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O′-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic 1H-NMR Study

Cited by 28 publications

References 78 publications

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Decanoic Acid and Not Octanoic Acid Stimulates Fatty Acid Synthesis in U87MG Glioblastoma Cells: A Metabolomics Study

NMR as a “Gold Standard” Method in Drug Design and Discovery

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