Publisher Correction: Fatty acid synthase, a novel poor prognostic factor for acute lymphoblastic leukemia which can be targeted by ginger extract

Harouni, Maryam Ghaeidamini; Rahgozar, Soheila; Babasheikhali, Somayeh Rahimi; Safavi, Arman; Ghodousi, Elaheh Sadat

doi:10.1038/s41598-020-78089-5

Cited by 3 publications

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“…The indispensability of lipid metabolism has been suggested to be a promising therapeutic target. Targeting FA biosynthesis and FA oxidation has been attempted in preclinical and clinical investigations, and both have encouraging outcomes against malignancies of T cells ( 13 , 23 , 104 , 209 ). The direct inhibition of cancer progression by targeting lipid metabolism as well as alleviation of chemo- and immunotherapy response has been demonstrated by various investigations ( 104 , 129 , 209 , 217 ).…”

Section: Discussionmentioning

confidence: 99%

“…Targeting FA biosynthesis and FA oxidation has been attempted in preclinical and clinical investigations, and both have encouraging outcomes against malignancies of T cells ( 13 , 23 , 104 , 209 ). The direct inhibition of cancer progression by targeting lipid metabolism as well as alleviation of chemo- and immunotherapy response has been demonstrated by various investigations ( 104 , 129 , 209 , 217 ). Considering the demonstrated as well as envisaged impact of lipid metabolism in T-cell malignancies, investigations exploring the connections between hallmark characters with the unambiguous arrangement in lipid metabolism are further warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of FASN in extra-nodal nasal NK/T-cell lymphoma cells was found to correlate with their survival adaptation ( 103 ). The upregulation of FASN in T-cell acute lymphoblastic leukemia (T-ALL) patient-derived cancer cells correlates with poor prognosis and drug susceptibility ( 104 ). With a murine model of T-cell lymphoma, FASN has been demonstrated to be a targetable enzyme that weakens the chemoresistant amplitude ( 13 , 105 ).…”

Section: Lipid Biosynthesis In T-cell Cancermentioning

confidence: 99%

“…Phytochemicals can suppress FASN leukemic cells. Ginger extract, gallic acid, cerulenin, and ginkgolic acids have demonstrated promising success in inhibiting leukemia cells by diminishing the FASN activity ( 104 , 211 , 212 ).…”

Section: Lipid Metabolism: a Novel Therapeutic Target For T-cell Mali...mentioning

confidence: 99%

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Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Mehta

Ratre

Soni³

et al. 2023

Front. Oncol.

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The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lipid Biosynthesis In T-cell Cancermentioning

confidence: 99%

Section: Lipid Metabolism: a Novel Therapeutic Target For T-cell Mali...mentioning

confidence: 99%

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Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Mehta

Ratre

Soni³

et al. 2023

Front. Oncol.

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“…In another study, molecular modeling analysis suggested that isogingerenone may bind to the fatty acid synthase enzyme, a marker protein in acute lymphoblastic leukemia ( 34 ). It has also been documented that this compound acts preferentially on senescent cells and thus has senolytic activity ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Streptomyces albidoflavus Q antifungal metabolites inhibit the ergosterol biosynthesis pathway and yeast growth in fluconazole-resistant Candida glabrata : phylogenomic and metabolomic analyses

Bautista-Crescencio,

Casimiro-Ramos,

Fragoso-Vázquez

et al. 2023

Microbiol Spectr

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There is an urgent need to develop new antifungals due to the increasing prevalence of multidrug-resistant fungal infections and the recent emergence of COVID-19-associated candidiasis. A good study model for evaluating new antifungal compounds is Candida glabrata , an opportunistic fungal pathogen with intrinsic resistance to azoles (the most common clinical drugs for treating fungal infections). The aim of the current contribution was to conduct in vitro tests of antifungal metabolites produced by the bacteria Streptomyces albidoflavus Q, identify their molecular structures, and utilize several techniques to provide evidence of their therapeutic target. S. albidoflavus was isolated from maize rhizospheric soil in Mexico and identified by phylogenomic analysis using a 92-gene core. Of the 66 metabolites identified in S. albidoflavus Q by a liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic analysis of the lyophilized supernatant, six were selected by the Way2drug server based on their in silico binding to the likely target, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR, the key enzyme in the ergosterol biosynthesis pathway). Molecular modeling studies show a relatively high binding affinity for the Cg HMGR enzyme by two secondary metabolites: isogingerenone B (diaryl heptanoid) and notoginsenoside J (polycyclic triterpene). These secondary metabolites were able to inhibit ergosterol synthesis and affect yeast viability in vitro . They also caused alterations in the ultrastructure of the yeast cytoplasmic membrane, as evidenced by transmission electron microscopy. The putative target of isogingerenone B and notoginsenoside J is distinct from that of azole drugs (the most common clinical antifungals). The target for the latter is the lanosterol 14 alpha-demethylase enzyme (Erg11). IMPORTANCE Multidrug resistance has emerged among yeasts of the genus Candida , posing a severe threat to global health. The problem has been exacerbated by the pandemic associated with COVID-19, during which resistant strains of Candida auris and Candida glabrata have been isolated from patients infected with the SARS-CoV-2 virus. To confront this challenge, the World Health Organization has invoked scientists to search for new antifungals with alternative molecular targets. This study identified 66 metabolites produced by the bacteria Streptomyces albidoflavus Q, 6 of which had promising properties for potential antifungal activity. The metabolites were tested in vitro as inhibitors of ergosterol synthesis and C. glabrata growth, with positive results. They were also found to damage the cytoplasmic membrane of the fungus. The corresponding molecular structures and their probable therapeutic target were established. The target is apparently distinct from that of azole drugs.

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Classification Technology and Application of Multifunctional Enzymes

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2021

CSA

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Publisher Correction: Fatty acid synthase, a novel poor prognostic factor for acute lymphoblastic leukemia which can be targeted by ginger extract

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 3 publications

References 0 publications

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Streptomyces albidoflavus Q antifungal metabolites inhibit the ergosterol biosynthesis pathway and yeast growth in fluconazole-resistant Candida glabrata : phylogenomic and metabolomic analyses

Classification Technology and Application of Multifunctional Enzymes

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