Analytical methods for the detection and characterization of unapproved phosphodiesterase type 5 inhibitors (PDE-5i) used in adulteration of dietary supplements- a review.

This article is an up-to-date review of 112 unapproved phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in sexual enhancement dietary supplements and other products from 2003 to July 2023. Seventy-five of these unapproved PDE-5i are analogues of sildenafil (67%), followed by 26 analogues of tadalafil (23%), 9 analogues of vardenafil (8%) and 2 other type of compounds (2%). The products have been formulated in various packaging, primarily in capsule, tablet, and powder forms. Common screening techniques allowing detection of such analogues include high performance or ultra-high performance liquid chromatography in tandem with ultra-violet detector (HPLC-UV or UPLC-UV) (50%) and thin-layer chromatography in tandem with ultra-violet detection (TLC-UV) (7%). Screening by mass spectrometry (MS) is relatively less common with the use of single-, triple-quadrupole or time-of-flight (TOF) mass spectrometers (9%). Meanwhile, the combined detection by UV-MS has been recorded at 10% usage. Screening by proton nuclear magnetic resonance spectroscopy (NMR) (11%) has also been applied. For compound characterization, i.e. structural elucidation, NMR spectroscopy has been preferred (100 out of 112 compounds), followed by high-resolution mass spectrometry (HRMS) (74 out of 112 compounds) and Fourier-transform infrared spectroscopy (FTIR) (44 out of 112 compounds). Over the past two decades, analytical technology has been evolving with enhanced sensitivity and resolution. Despite this, structural elucidation of the new emerging analogues in adulterated dietary supplements remains a challenge, especially when the analogues involve complex structural modification. Therefore, the above-mentioned techniques may not be adequate to characterize the analogues. Additional work involving chiroptical methods, two-dimensional (2D) NMR experiments and X-ray crystallography are likely to be required in the future.

Modulation of the crystallization of rapeseed oil using lipases and the impact on ice cream properties.

We investigated the possibility to use rapeseed as a main oil in ice cream formulations by changing its functionality when using different kinds of lipases. Through a 24 h-emulsification and a centrifugation, the modified oils were further used as functional ingredients. All lipolysis was first assessed as a function of time by 13C NMR, where triglycerides consumption and the formation of low-molecular polar lipids (LMPL: monoacylglycerol and free fatty acids, FFAs) were selectively identified and compared. The more the FFAs, the sooner the crystallization (from -55 to -10 °C) and the later the melting temperatures (from -17 to 6 °C) measured by differential scanning calorimetry. These modifications were exploited in ice cream formulations with a significant impact on overall hardness (range of 60-216 N) and flowing during defrosting (from 1.29 to 0.35g/min). The global behavior of products can be controlled by the composition of LMPL within oil.

The POWER saga from 2007 to 2022: An example of a sexual enhancement dietary supplement tainted by different adulterants and still on the market.

Ten POWER dietary supplements, chronologically called tabs, pills then caps, and advertised as 100% natural aphrodisiacs, were analyzed by 1H NMR from 2007 to 2022. They were all tainted by PDE-5 inhibitors. Eight different adulterants were identified (sildenafil (1), sildenafil analogues (6), and vardenafil analogue (1)). Their amounts ranged from 15 to 145 mg/capsule. Four supplements contained at least 100 mg/capsule of PDE-5 inhibitor or analogue, the maximal recommended dose of sildenafil. The nature of the adulterant has changed over time, probably to evade its detection by regulatory agencies routine screening tests. Despite several warnings and/or seizures from several European food and/or health authorities, the dietary supplement POWER is still on sale on the Internet, thus demonstrating the impossibility of controlling this market. Faced with this situation, the consumer should be better informed by establishing at the European level a public database of tainted dietary supplements on the model of that of the US Food and Drug Administration. It should indicate the product name, its photo, the adulterant name, and be easily accessible to everyone.

Quality evaluation of berberine food supplements with high-field and compact 1H NMR spectrometers.

Due to their health benefits, including regulating blood sugar and lowering cholesterol, berberine food supplements (FS) are widely used by consumers. This study aims to evaluate the quality of such products by proposing a new analytical methodology based on low-field NMR. Eighteen berberine FS were analyzed with both conventional (500 MHz) and benchtop (60 MHz) NMR spectrometers. Three quantitative 60 MHz 1H NMR methodologies were performed to determine berberine contents that were compared to those obtained at 500 MHz considered as reference measurements. To make the recording time of the spectra acquired at low field compatible with the requirements of a routine control, the quantification was carried out using a calibration curve established under conditions of incomplete relaxation of BrB protons. This methodology, applied to a test sample of 15 mg of FS, allowed to accurately measure a minimum quantity of berberine of ≈ 10 mg/capsule or tablet in 15 min. Regarding the FS, their labels are often unclear and/or incomplete for the consumer. Moreover, only 56 % of the FS analyzed actually contain the claimed quantity of berberine. The amounts of active they supply per day are extremely variable with only 39 % of the FS delivering a sufficient dose to achieve a hypoglycemic or hypolipidemic effect (1000-1500 mg/day based on literature data). These results show that health authorities should institute much stricter control and regulation over the production, labeling and marketing of berberine-based FS.

Quality assessment of Curcuma dietary supplements: Complementary data from LC-MS and 1H NMR.

Due to the numerous potential health benefits of Curcuma, turmeric dietary supplements (DS) are among the top selling products. To assess the quality of these formulations, thirty Curcuma DS along with five standard Curcuma rhizomes were analyzed with UHPLC-MS and 1H NMR. The chemometric treatment of the UHPLC-MS spectra showed a significant variability of their chemical composition that was confirmed by 1H NMR which allowed the absolute quantification of the Curcuma major bioactive components, i.e. curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin), and turmerones (aryl-, α- and ß-) as well as piperine, a commonly associated curcumin bioavailability enhancer: respectively 3.5-556, 0-8.6, 0.18-8.1 mg/capsule or tablet. The comparison of the actual and claimed quantities of curcuminoids and piperine showed that 58% of the DS contained the expected amounts of actives.

Study of rapeseed oil gelation induced by commercial monoglycerides using a chemometric approach.

Commercial oleogelators rich in monoglycerides (MGs) are complex mixtures of acylglycerides with variable gelling properties, depending on the oil used and their concentration. In this study we developed a chemometric approach to identify the key parameters involved in gelling process. Analytical parameters have been defined, using GC and NMR analysis to identify fatty acids and acylglycerides composing the mixtures. Specific acylglyceride families and compound ratios were calculated to streamline the analytical results. To determine the key analytical parameters, artificial neural networks were used in a QSPR study related to the gelling properties measured by rheology through oscillatory experiments. At low oleogelator concentrations, the MGs especially rich in C16:0 and the ratio of specific isomers both have a positive influence on G'. For high oleogelator concentrations, C18:0-rich acylglycerides and unsaturated/saturated fatty acid ratios have a positive influence on G'. Conversely, at low concentrations, C18:0-rich acylglycerides show a lesser effect on G'.

Hepatocyte nuclear factor-1ß shapes the energetic homeostasis of kidney tubule cells.

Energetic metabolism controls key steps of kidney development, homeostasis, and epithelial repair following acute kidney injury (AKI). Hepatocyte nuclear factor-1ß (HNF-1ß) is a master transcription factor that controls mitochondrial function in proximal tubule (PT) cells. Patients with HNF1B pathogenic variant display a wide range of kidney developmental abnormalities and progressive kidney fibrosis. Characterizing the metabolic changes in PT cells with HNF-1ß deficiency may help to identify new targetable molecular hubs involved in HNF1B-related kidney phenotypes and AKI. Here, we combined 1 H-NMR-based metabolomic analysis in a murine PT cell line with CrispR/Cas9-induced Hnf1b invalidation (Hnf1b-/- ), clustering analysis, targeted metabolic assays, and datamining of published RNA-seq and ChIP-seq dataset to identify the role of HNF-1ß in metabolism. Hnf1b-/- cells grown in normoxic conditions display intracellular ATP depletion, increased cytosolic lactate concentration, increased lipid droplet content, failure to use pyruvate for energetic purposes, increased levels of tricarboxylic acid (TCA) cycle intermediates and oxidized glutathione, and a reduction of TCA cycle byproducts, all features consistent with mitochondrial dysfunction and an irreversible switch toward glycolysis. Unsupervised clustering analysis showed that Hnf1b-/- cells mimic a hypoxic signature and that they cannot furthermore increase glycolysis-dependent energetic supply during hypoxic challenge. Metabolome analysis also showed alteration of phospholipid biosynthesis in Hnf1b-/- cells leading to the identification of Chka, the gene coding for choline kinase α, as a new putative target of HNF-1ß. HNF-1ß shapes the energetic metabolism of PT cells and HNF1B deficiency in patients could lead to a hypoxia-like metabolic state precluding further adaptation to ATP depletion following AKI.

Synthetic cannabinoids in e-liquids: A proton and fluorine NMR analysis from a conventional spectrometer to a compact one.

The 1H NMR profiles of 13 samples of e-liquids supplied by French customs were obtained with high-field and low-field NMR. The high-field 1H NMR spectra allowed the detection of matrix signals, synthetic cannabinoids, and flavouring compounds. Quantitative results were obtained for the five synthetic cannabinoids detected: JWH-210, 5F-MDMB-PICA, 5F-ADB, 5F-AKB48, and ADB-FUBINACA. Conventional GC-MS analysis was used to confirm compound identification. Fluorine-19 NMR was proposed for the quantification of fluorinated synthetic cannabinoids and was successfully implemented on both 400 MHz and 60 MHz NMR spectrometers. This study based on few examples explored the potentiality of low-field NMR for quantitative and quantitative analysis of synthetic cannabinoids in e-liquids.

Isolation and identification of ten new sildenafil derivatives in an alleged herbal supplement for sexual enhancement.

A sexual enhancer dietary supplement in pre-commercialization phase was analyzed. It contained the two phosphodiesterase-5 inhibitors (PDE-5i) sildenafil and methisosildenafil as major adulterants. Fourteen more sildenafil derivatives were detected and after isolation, their structures were elucidated thanks to NMR, high resolution and tandem mass spectrometry, and UV spectroscopy. Ten of them were never described. All these compounds are probably by-products of different reaction steps during the synthesis of the two PDE-5i that were not properly eliminated during the purification procedure. The total amount of sildenafil-related compounds was estimated at 68 mg per capsule, sildenafil and methisosildenafil accounting for 20 mg and 38 mg respectively.

Chemometric Analysis of Low-field 1H NMR Spectra for Unveiling Adulteration of Slimming Dietary Supplements by Pharmaceutical Compounds.

The recent introduction of compact or low-field (LF) NMR spectrometers that use permanent magnets, giving rise to proton (1H) NMR frequencies between 40 and 80 MHz, have opened up new areas of application. The two main limitations of the technique are its insensitivity and poor spectral resolution. However, this study demonstrates that the chemometric treatment of LF 1H NMR spectral data is suitable for unveiling medicines as adulterants of slimming dietary supplements (DS). To this aim, 66 DS were analyzed with LF 1H NMR after quick and easy sample preparation. A first PLS-DA model built with the LF 1H NMR spectra from forty DS belonging to two classes of weight-loss DS (non-adulterated, and sibutramine or phenolphthalein-adulterated) led to the classification of 13 newly purchased test samples as natural, adulterated or borderline. This classification was further refined when the model was made from the same 40 DS now considered as representing three classes of DS (non-adulterated, sibutramine-adulterated, and phenolphthalein-adulterated). The adulterant (sibutramine or phenolphthalein) was correctly predicted as confirmed by the examination of the 1H NMR spectra. A limitation of the chemometric approach is discussed with the example of two atypical weight-loss DS containing fluoxetine or raspberry ketone.

Comparative Chemical Profiling and Monacolins Quantification in Red Yeast Rice Dietary Supplements by 1H-NMR and UHPLC-DAD-MS.

Red yeast rice dietary supplements (RYR DS) are largely sold in Western countries for their cholesterol-lowering/regulating effect due to monacolins, mainly monacolin K (MK), which is, in fact, lovastatin, the first statin drug on the market. 1H-NMR was used as an easy, rapid and accurate method to establish the chemical profiles of 31 RYR DS and to quantify their monacolin contents. Among all the 1H resonances of the monacolins found in RYR, only those of the ethylenic protons of the hexahydronaphthalenic ring at 5.84 and 5.56 ppm are suitable for quantification because they show no overlap with the matrix signals. The total content in monacolins per capsule or tablet determined in 28 DS (the content in 3 DS being below the limit of quantification of the method, ≈ 0.25 mg per unit dose) was close to that measured by UHPLC, as shown by the good linear correlation between the two sets of values (slope 1.00, y-intercept 0.113, r2 0.986). Thirteen of the 31 RYR DS analyzed (i.e., 42%) did not provide label information on the concentration of monacolins and only nine of the 18 formulations with an indication (i.e., 50%) actually contained the declared amount of monacolins.

Urinary metabolomic signature of muscle-invasive bladder cancer: A multiplatform approach.

Bladder cancer (BCa) is ninth amongst the most common types of cancer in the human population worldwide. The statistics of incidence and mortality of BCa are alarming and the currently applied diagnostic methods are still not sensitive enough. This leads to a large number of undiagnosed BCa cases, usually among patients in the early stages of the disease. Despite the fact that many risk factors of BCa have been recognized, the pathomechanism of development of bladder cancer has not been fully explained yet. Therefore, in the present study, multiplatform urinary metabolomics has been implemented in order to scrutinize potential diagnostic indicators of BCa that might help to explain its pathomechanism and be potentially useful in diagnosis and determination of stage of the disease. Urine samples collected from muscle-invasive high grade BCa patients (n = 24) and healthy volunteers (n = 24) were matched in terms of most common BCa risk factors i.e. gender, age, BMI and smoking status. They were analyzed by high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) using RP and HILIC chromatography, gas chromatography hyphenated with triple quadruple mass spectrometry detection (GC-QqQ/MS) in scan mode, and proton nuclear magnetic resonance (1H NMR). The six datasets obtained were submitted to univariate and multivariate statistical analyses. 17 metabolites significantly discriminated urinary profiles of BCa patients from urinary profiles of healthy volunteers. These metabolites are mainly involved in amino acid metabolism, pyrimidine and purine metabolism, as well as energy metabolism and might play a crucial role in the pathogenesis of BCa.

NMR-Based Μetabolomics of the Lipid Fraction of Organic and Conventional Bovine Milk.

Origin and quality identification in dairy products is an important issue and also an extremely challenging and complex experimental procedure. The objective of the present work was to compare the metabolite profile of the lipid fraction of organic and conventional bovine milk using NMR metabolomics analysis. ¹H-NMR and 1D TOCSY NMR methods of analysis were performed on extracted lipid fraction of lyophilized milk. For this purpose, 14 organic and 16 conventional retail milk samples were collected monthly, and 64 bulk-tank (58 conventional and 6 organics) milk samples were collected over a 14-month longitudinal study in Cyprus. Data were treated with multivariate methods (PCA, PLS-DA). Minor components were identified and quantified, and modification of the currently used equations is proposed. A significantly increased % content of conjugated (9-cis, 11-trans)18:2 linoleic acid (CLA), α-linolenic acid, linoleic acid, allylic protons and total unsaturated fatty acids (UFA) and decreased % content for caproleic acid were observed in the organic samples compared to the conventional ones. The present work confirms that lipid profile is affected by contrasting management system (organic vs. conventional), and supports the potential of NMR-based metabolomics for the rapid analysis and authentication of the milk from its lipid profile.

Benchtop low-field 1H Nuclear Magnetic Resonance for detecting falsified medicines.

Falsified medicines represent a serious threat to public health. Among the different measures to effectively combat this scourge, analytical methods play a key role in their detection and removal from the market before they reach patients. The present study evaluates for the first time the potential of a benchtop low-field (LF) Nuclear Magnetic Resonance (NMR) spectrometer for uncovering drug falsification by focusing on the analysis of fifteen erectile dysfunction and nine antimalarial medicines, the most commonly reported falsified medicines in developed and developing countries respectively. After a simple and rapid sample preparation and ≈ 5 min of spectrum recording, LF 1H NMR allows to conclude on the quality of the medicine: presence or absence of the expected active pharmaceutical ingredient (API), presence of unexpected API, absence of any API. Some 2D experiments are also described but although conclusive they are hampered by the duration of the experiments. The LF 1H NMR assay, based on the internal standard method, is validated by the determination of its accuracy, repeatability, limits of detection (LOD) and quantification (LOQ), and by comparison of the data obtained on some medicines after 45 min of spectrum recording to those measured with high-field 1H NMR. Because of its saving capabilities (cost, space, user experience), LF 1H NMR spectroscopy might become a routine screening tool in laboratories in charge of detecting falsified medicines.

Diffusion-ordered spectroscopy on a benchtop spectrometer for drug analysis.

The first reported two-dimensional diffusion-ordered spectroscopy (DOSY) experiments were recorded at low field (LF) on a benchtop NMR spectrometer using the BPP-STE-LED (bipolar pulse pair-stimulated echo sequence with a longitudinal eddy current delay) pulse sequence which limits phase anomalies and baseline discrepancies. A LF DOSY map was first obtained from a solution of a model pharmaceutical formulation containing a macromolecule and an active pharmaceutical ingredient. It revealed a clear separation between the components of the mixture and gave apparent diffusion coefficients (ADC) values consistent with those measured from the reference high field experiment. LF DOSY was then applied to a real esomeprazole medicine and several gradient sampling schemes (linear, exponential and semi-gaussian (SG)) were compared. With a pulsed field gradient range of 4-70%, the most reliable results were given by the SG ramp. The resulting LF DOSY map obtained after 2.84 h of acquisition confirmed that the diffusion dimension is of prime interest to facilitate the assignment of overcrowded LF spectra although relevant ADC values could not be obtained in part of the spectrum with highly overlapped signals.

Glucose metabolism and NRF2 coordinate the antioxidant response in melanoma resistant to MAPK inhibitors.

Targeted therapies as BRAF and MEK inhibitor combination have been approved as first-line treatment for BRAF-mutant melanoma. However, disease progression occurs in most of the patients within few months of therapy. Metabolic adaptations have been described in the context of acquired resistance to BRAF inhibitors (BRAFi). BRAFi-resistant melanomas are characterized by an increase of mitochondrial oxidative phosphorylation and are more prone to cell death induced by mitochondrial-targeting drugs. BRAFi-resistant melanomas also exhibit an enhancement of oxidative stress due to mitochondrial oxygen consumption increase. To understand the mechanisms responsible for survival of BRAFi-resistant melanoma cells in the context of oxidative stress, we have established a preclinical murine model that accurately recapitulates in vivo the acquisition of resistance to MAPK inhibitors including several BRAF or MEK inhibitors alone and in combination. Using mice model and melanoma cell lines generated from mice tumors, we have confirmed that the acquisition of resistance is associated with an increase in mitochondrial oxidative phosphorylation as well as the importance of glutamine metabolism. Moreover, we have demonstrated that BRAFi-resistant melanoma can adapt mitochondrial metabolism to support glucose-derived glutamate synthesis leading to increase in glutathione content. Besides, BRAFi-resistant melanoma exhibits a strong activation of NRF-2 pathway leading to increase in the pentose phosphate pathway, which is involved in the regeneration of reduced glutathione, and to increase in xCT expression, a component of the xc-amino acid transporter essential for the uptake of cystine required for intracellular glutathione synthesis. All these metabolic modifications sustain glutathione level and contribute to the intracellular redox balance to allow survival of BRAFi-resistant melanoma cells.

A review of synthetic phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in dietary supplements.

To date, there are 80 synthetic PDE-5i found as adulterants in dietary supplements. Analogues of sildenafil remain as the top list with 50 (62%) and are followed by analogues of tadalafil, 21 (26%), analogues of vardenafil, 7 (9%) and others, 2 (3%). The sildenafil group can be sub-categorized into sulphonamide-bonded (24, 48%), acetyl-bonded (11, 22%), carbonyl or thiocarbonyl-bonded (8, 16%) and other types (7, 14%) based on the functional group linked to pyrazolopyrimidine-one moieties. Meanwhile, analogues of tadalafil have become popularly found as adulterants in dietary supplements like beverages and herbal extracts from 2015 to 2016. The uptrend has been observed with the increase in number and complexity with more trans-oriented and dimerized tadalafil analogues being reported. Interestingly, there is no much increase for analogues of vardenafil. About two thirds of analogues have been reported from the Asian countries (67%), followed by Europe (22%) and North America (11%). South Korea and Singapore have reported the most number of analogues with a total number of 40 (50%). One plausible contributing factor to this trend is the convenient purchase of sexual enhancement dietary supplements, especially the on-line purchase. In terms of analytical methodologies, high performance liquid chromatography (HPLC) hyphenated to ultra-violet (UV) and/or mass spectrometry (MS) detection have been preferred in the screening analysis, i.e. 70 out of 77 compounds have been analysed by HPLC-UV. In addition, the electrospray ionization multistage fragmentation experiments (ESI-MSn) for acquiring low- and high-resolution mass spectra have been successfully applied to detect and quantify PDE-5i in adulterated products simultaneously. Nuclear magnetic resonance (NMR) is another important technique in the structural elucidation of novel analogues.

Screening of "spice" herbal mixtures: From high-field to low-field proton NMR.

Forty one samples of herbal spices intended to be introduced into the European market and seized by the French customs were analysed with high-field 1H NMR. Nine synthetic cannabinoids (MAM-2201, JWH-073, JWH-210, JWH-122, JWH-081, JWH-250, UR-144, XLR-11 and AKB-48-5F) were detected and quantified. The ability of a compact benchtop low-field NMR spectrometer for a rapid screening of the content of herbal blends was then successfully explored for the first time. Even if low-field 1H NMR spectra are much less resolved than high-field spectra, we demonstrate that they provide valuable clues on the chemical structures of synthetic cannabinoids with the detection of some typical signals.

Role of Medicines of Unknown Identity in Adverse Drug Reaction-Related Hospitalizations in Developing Countries: Evidence from a Cross-Sectional Study in a Teaching Hospital in the Lao People's Democratic Republic.

INTRODUCTION: The health dangers of medicines of unknown identity (MUIs) [loose pharmaceutical units repackaged in individual bags without labelling of their identity] have been suspected in L/MICs. Using visual and analytical tools to identify MUIs, we investigated the frequency of, and factors associated with, adverse drug reaction (ADR)-related hospitalizations in a central hospital in Vientiane Capital, Lao People's Democratic Republic (PDR). METHODS: All unplanned admissions, except for acute trauma and intentional overdose, were prospectively recorded during a 7-week period in 2013, leading to include 453 adults hospitalized for ≥24 h. The patients or their relatives were interviewed to complete the study questionnaire. MUIs suspected of being involved in ADR(s) were identified through comparison of visual characteristics of tablets/capsules with that of reference medicines (photograph tool), and by proton nuclear magnetic resonance and mass spectrometry analyses. Factors associated with ADRs were identified by multivariate logistic regression. RESULTS: The frequency of hospitalizations related to an ADR was 5.1% (23/453, 95% confidence interval [CI] 3.1-7.1). Forty-eight (12.8%) patients used MUI(s) in the last 2 weeks preceding hospitalization. They were more likely to be hospitalized because of an ADR (adjusted odds ratio 4.5, 95% CI 1.7-11.5) than patients using medicines of known identity. MUIs were mainly involved in bleeding gastroduodenal ulcers. The photograph tool led to the misidentifications because of look-alike pharmaceutical units in the medicines photograph collection. CONCLUSION: According to the results of this study, there is a need to ensure appropriate labelling of medicines at dispensing and to provide well-suited tools to identify MUIs in clinical settings to improve drug safety and patients' care in developing countries with limited capacities for drug analysis.

Metabolic rewiring in cancer cells overexpressing the glucocorticoid-induced leucine zipper protein (GILZ): Activation of mitochondrial oxidative phosphorylation and sensitization to oxidative cell death induced by mitochondrial targeted drugs.

Cancer cell metabolism is largely controlled by oncogenic signals and nutrient availability. Here, we highlighted that the glucocorticoid-induced leucine zipper (GILZ), an intracellular protein influencing many signaling pathways, reprograms cancer cell metabolism to promote proliferation. We provided evidence that GILZ overexpression induced a significant increase of mitochondrial oxidative phosphorylation as evidenced by the augmentation in basal respiration, ATP-linked respiration as well as respiratory capacity. Pharmacological inhibition of glucose, glutamine and fatty acid oxidation reduced the activation of GILZ-induced mitochondrial oxidative phosphorylation. At glycolysis level, GILZ-overexpressing cells enhanced the expression of glucose transporters in their plasmatic membrane and showed higher glycolytic reserve. 1H NMR metabolites quantification showed an up-regulation of amino acid biosynthesis. The GILZ-induced metabolic reprograming is present in various cancer cell lines regardless of their driver mutations status and is associated with higher proliferation rates persisting under metabolic stress conditions. Interestingly, high levels of OXPHOS made GILZ-overexpressing cells vulnerable to cell death induced by mitochondrial pro-oxidants. Altogether, these data indicate that GILZ reprograms cancer metabolism towards mitochondrial OXPHOS and sensitizes cancer cells to mitochondria-targeted drugs with pro-oxidant activities.