Detection of Metabolite Changes in C6 Glioma Cells Cultured with Antimitotic Oleyl Glycoside by <sup>1</sup>H MAS NMR

García‐Álvarez, Isabel; Garrido, Leoncio; Doncel‐Pérez, Ernesto; Nieto–Sampedro, Manuel; Fernández-Mayoralas, Alfonso

doi:10.1021/jm8012807

Cited by 17 publications

(19 citation statements)

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“…The favorable effect of an oleyl chain on the antitumor activity was also observed in a family of alkylated iminosugars [6]. Further studies [7,8] designed to understand the mechanism behind the activity of 1 on lung carcinoma A549 and glioma C6 cells showed that, at concentrations above 30 µM, glycoside 1 drastically altered the cell lipid profile, with a significant increase in sphingolipid and glycosphingolipid levels, that eventually resulted in cell death [8]. Despite its promising activity against cancer cells in culture, glycoside 1 was inactive when tested in mice bearing an implanted C6 glioma.…”

Section: Introductionmentioning

confidence: 89%

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

et al. 2013

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The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning (1H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the 1H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death.

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Section: Introductionmentioning

confidence: 89%

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

et al. 2013

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“…While numerous HRMAS‐based studies have investigated well established chemotherapeutics, such as cisplatin, methotrexate (MTX), doxorubicin, tamoxifen, tyrosine kinase inhibitors, and bevacizumab—mostly focused on providing a more detailed understanding of the drugs' mechanisms of action and intracellular processes triggered by these drugs, such as apoptosis—others have explored the possibilities of new agents …”

Section: Evaluating Therapy Responsesmentioning

confidence: 99%

“…As mentioned above, HRMAS has also been used to study and develop new anti‐cancer agents and investigate their therapeutic efficacy against different cancer types …”

Section: Evaluating Therapy Responsesmentioning

confidence: 99%

Applications of high‐resolution magic angle spinning MRS in biomedical studies I—cell line and animal models

et al. 2017

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Summary High-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS) allows for direct measurements of non-liquid tissue and cell specimens to present valuable insights of the cellular metabolisms of physiological and pathological processes. HRMAS produces high resolution spectra comparable to those obtained from solutions of specimen extracts but without complex metabolite extraction processes, and preserves the tissue cellular structure suitable for pathological examinations following spectroscopic analysis. The technique has been applied in a wide variety of biomedical and biochemical studies and become one of the major platforms of metabolomic studies. By quantifying single metabolites, metabolite ratios or metabolic profiles in their entirety, HRMAS presents promising possibilities for diagnosis and prediction of clinical outcomes for various diseases, as well as deciphering of metabolic changes resulting from drug therapies or xenobiotic interactions. In this review, we evaluate HRMAS MRS results on animal models and cell lines reported in literature, and present the diverse applications of the method for the understanding of pathological processes, the effectiveness of therapies, the developments of disease animal models, and the new progresses in the HRMAS methodology.

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“…The results obtained indicated that the activity was increased by a long hydrocarbon chain at position C-1 of the glucosamine backbone, the most inhibitory compound being the oleyl glycoside 2 (Chart 1). To obtain information about its mode of action, metabolite changes in C6 glioma cells were analyzed after treatment with glycoside 2, using high-resolution magic angle spinning (HR-MAS) 1 H NMR 371. The data obtained from the 1 H NMR spectra of the different experiments suggest that glycoside 2 inhibited cell division (IC 50 approx.…”

Section: Making Glioma Immunodetectablementioning

confidence: 99%

“…Determination of the precise structure of neurostatin required the purification of comparatively large amounts of the molecule. The fractionation of the amounts of brain tissue required was facilitated by preparation of ganglioside extracts 371. Neurostatin was purified from such extracts, using a combination of conventional and high performance ion-exchange and reverse phase chromatographies 357.…”

Section: Making Glioma Immunodetectablementioning

confidence: 99%

Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System

Nieto–Sampedro

Valle-Argos

Gómez-Nicola

et al. 2011

Clin Med Insights Oncol

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Treated glioblastoma patients survive from 6 to 14 months. In the first part of this review, we describe glioma origins, cancer stem cells and the genomic alterations that generate dysregulated cell division, with enhanced proliferation and diverse response to radiation and chemotherapy. We review the pathways that mediate tumour cell proliferation, neo-angiogenesis, tumor cell invasion, as well as necrotic and apoptotic cell death. Then, we examine the ability of gliomas to evade and suppress the host immune system, exhibited at the levels of antigen recognition and immune activation, limiting the effective signaling between glioma and host immune cells.The second part of the review presents current therapies and their drawbacks. This is followed by a summary of the work of our laboratory during the past 20 years, on oligosaccharide and glycosphingolipid inhibitors of astroblast and astrocytoma division. Neurostatins, the O-acetylated forms of gangliosides GD1b and GT1b naturally present in mammalian brain, are cytostatic for normal astroblasts, but cytotoxic for rat C6 glioma cells and human astrocytoma grades III and IV, with ID50 values ranging from 200 to 450 nM. The inhibitors do not affect neurons or fibroblasts up to concentrations of 4 μM or higher.At least four different neurostatin-activated, cell-mediated antitumoral processes, lead to tumor destruction: (i) inhibition of tumor neovascularization; (ii) activation of microglia; (iii) activation of natural killer (NK) cells; (iv) activation of cytotoxic lymphocytes (CTL). The enhanced antigenicity of neurostatin-treated glioma cells, could be related to their increased expression of connexin 43. Because neurostatins and their analogues show specific activity and no toxicity for normal cells, a clinical trial would be the logical next step.

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Detection of Metabolite Changes in C6 Glioma Cells Cultured with Antimitotic Oleyl Glycoside by ¹H MAS NMR

Cited by 17 publications

References 32 publications

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

Applications of high‐resolution magic angle spinning MRS in biomedical studies I—cell line and animal models

Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System

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Detection of Metabolite Changes in C6 Glioma Cells Cultured with Antimitotic Oleyl Glycoside by 1H MAS NMR

Cited by 17 publications

References 32 publications

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

Applications of high‐resolution magic angle spinning MRS in biomedical studies I—cell line and animal models

Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System

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Detection of Metabolite Changes in C6 Glioma Cells Cultured with Antimitotic Oleyl Glycoside by ¹H MAS NMR