Hexose Transporters in Cancer: From Multifunctionality to Diagnosis and Therapy

Echeverría, Carolina E.; Nualart, Francisco; Ferrada, Luciano; Smith, Gary J.; Godoy, Alejandro

doi:10.1016/j.tem.2020.12.006

Cited by 19 publications

(20 citation statements)

References 99 publications

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“…Mannose‐6‐phosphate (Man‐6‐P) is converted to fructose 6‐P‐phosphate (Fru‐6‐P) by PMI, at which point it joins glycolysis (Figure 2C ). 12 We analyzed the expression of HK and PMI in AML cell lines. PMI was expressed in all leukemia cell lines and positively correlated with mannose metabolic activity (Figures 2D and S2A ).…”

Section: Resultsmentioning

confidence: 99%

“…Mannose is a monosaccharide incorporated into cells through glucose transporters. 12 In pancreatic cancer and colorectal cancer, which express a low level of PMI, dietary mannose inhibits cancer cell growth and increases chemosensitivity of cisplatin and doxorubicin. 13 By contrast, leukemia cells express a high level of PMI, and the role of mannose metabolism in energy metabolism remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia

et al. 2021

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Leukemia cell proliferation requires activation and reprogramming of metabolic pathways to supply anabolic cell growth. This aberrant cancer metabolism was first recognized by Warburg, 1 who postulated that cancer tissues have a higher rate of glucose uptake and glycolysis compared with normal tissues and rely primarily on glucose to produce ATP with or without oxygen. Oncogenic driver genes regulate metabolic pathways such as MYC and RAS, which drive metabolic reprogramming in leukemia. Elevated MYC expression is a hallmark of Burkitt's lymphoma and acute lymphoblastic leukemias (ALL). Aberrant activation of MYC leads to increased glucose uptake and glycolytic activity, glutaminolysis, and lipid synthesis. [2][3][4][5] Activating mutations in the RAS pathway are characteristic of

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia

et al. 2021

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“…Fourteen GLUT proteins, including GLUT 1-12, myoinositol transporter (HMIT) and GLUT 14, are expressed in humans [ 27 ]. Both glucose and insulin are potent enhancers of hippocampal memory processes and it has been suggested that insulin’s cognitive effects may occur via upregulation in GLUT4-mediated glucose uptake [ 28 ]. Indeed, GLUT4 is responsible for the majority of the circulating blood glucose clearance and uptake into skeletal muscle, liver and fat cells.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, GLUT4 is responsible for the majority of the circulating blood glucose clearance and uptake into skeletal muscle, liver and fat cells. GLUT4 is insulin-sensitive and upon insulin stimulation, GLUT4 is translocated to the PM from intracellular vesicular [ 28 ]. However, this process is diminished in insulin resistance and diabetes type 2.…”

Section: Discussionmentioning

confidence: 99%

Isolation, Identification and Pharmacological Effects of Mandragora autumnalis Fruit Flavonoids Fraction

et al. 2022

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Since ancient times, Mandragora autumnalis has been used as a traditional medicinal plant for the treatment of numerous ailments. In light of this, the current study was designed to isolate and identify the chemical constituents of the flavonoids fraction from M. autumnalis ripe fruit (FFM), and evaluate its DPPH scavenging, anti-lipase, cytotoxicity, antimicrobial and antidiabetic effects. An ethyl acetate extract of M. autumnalis was subjected to a sequence of silica gel column chromatography using different eluents with various polarities. The chemical structures of the isolated compounds were identified using different spectral techniques, including 1H NMR and 13C NMR. FFM’s anti-diabetic activity was assessed using a glucose transporter-4 (GLUT4) translocation assay, as well as an inhibition against α-amylase and α-glucosidase using standard biochemical assays. The FFM anti-lipase effect against porcine pancreatic lipase was also evaluated. Moreover, FFM free radical scavenging activity using the DPPH test and antimicrobial properties against eight microbial strains using the micro-dilution method were also assessed. Four flavonoid aglycones were separated from FFM and their chemical structures were identified. The structures of the isolated compounds were established as kaempferol 1, luteolin 2, myricetin 3 and (+)-taxifolin 4, based on NMR spectroscopic analyses. The cytotoxicity test results showed high cell viability (at least 90%) for up to 1 mg/mL concentration of FFM, which is considered to be safe. A dose-dependent increase in GLUT4 translocation was significantly shown (p < 0.05) when the muscle cells were treated with FFM up to 0.5 mg/mL. Moreover, FFM revealed potent α-amylase, α-glucosidase, DPPH scavenging and porcine pancreatic lipase inhibitory activities compared with the positive controls, with IC50 values of 72.44 ± 0.89, 39.81 ± 0.74, 5.37 ± 0.41 and 39.81 ± 1.23 µg/mL, respectively. In addition, FFM inhibited the growth of all of the tested bacterial and fungal strains and showed the greatest antibacterial activity against the K. pneumoniae strain with a MIC value of 0.135 µg/mL. The four flavonoid molecules that constitute the FFM have been shown to have medicinal promise. Further in vivo testing and formulation design are needed to corroborate these findings, which are integral to the pharmaceutical and food supplement industries.

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“…Role of vitamin C along with hexose transporters ( Gluts) have been the subject of interest in cancer treatment as well. Vitamin C exist in reduced and oxidized forms; namely ascorbic acid and dehydroascorbic acid( DHA).Gluts and DHA have been proposed as potential targets for synergistic pharmacological targets in certain cancers (3). Data emanating from the efficacy of vitamin C in sepsis has sparked enthusiasm in a significant quarter of medical professionals.…”

mentioning

confidence: 99%

Interaction between vitamin C and point of care glucose monitoring. are we overly wary of it or is it a valid concern?

Surani

Sharma²

2021

Current Medical Research and Opinion

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Hexose Transporters in Cancer: From Multifunctionality to Diagnosis and Therapy

Cited by 19 publications

References 99 publications

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia

Isolation, Identification and Pharmacological Effects of Mandragora autumnalis Fruit Flavonoids Fraction

Interaction between vitamin C and point of care glucose monitoring. are we overly wary of it or is it a valid concern?

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