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Title[redir]:
A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo | Cell Death & Disease
Description:
Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here we demonstrate that the natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP. Polydatin blocks G6PD causing accumulation of reactive oxygen species and strong increase of endoplasmic reticulum stress. These effects are followed by cell cycle block in S phase, an about 50% of apoptosis, and 60% inhibition of invasion in vitro. Accordingly, in an orthotopic metastatic model of tongue cancer, 100 mg/kg polydatin induced an about 30% tumor size reduction with an about 80% inhibition of lymph node metastases and 50% reduction of lymph node size (p < 0.005). Polydatin is not toxic in animals up to a dose of 200 mg/kg and a phase II clinical trial shows that it is also well tolerated in humans (40 mg twice a day for 90 days). Thus, polydatin may be used as a reliable tool to limit human cancer growth and metastatic spread.
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Keywords {🔍}
cell, polydatin, cells, pubmed, cancer, article, gpd, google, scholar, fig, cas, treatment, stress, assay, central, analysis, lymph, performed, nature, usa, cycle, effects, treated, control, mice, data, ppp, apoptosis, inhibition, tumor, death, pathway, invasion, phosphate, growth, node, metastases, nadph, effect, dehydrogenase, proliferation, vivo, protein, italy, min, pentose, viability, mcfgpd, inhibits, increase,
Topics {✒️}
nature portfolio supplementary table 2 privacy policy trans-resveratrol 3-β-mono-d-glucoside high-rate pentose-phosphate pathways diffuse large-b-cell lymphoma campania regional government negative control pcmv3-untagged-ncv advertising combination index nature 459 nature 527 nature spectral library construction reprints 5-trihydroxystilbene-3-β-d-glucoside glucose-6-phosphate dehydrogenase activity oneomics confidence threshold including glucose-6-phosphate dehydrogenase cancer research glucose-6-phosphate dehydrogenase inhibition china micronized palmitoylethanolamide/trans-polydatin treatment ymc triart-c18 column targeting cancer metabolism--aiming inhibiting lkb1-ampk signalling education research central carbon metabolism carcinogen-induced murine model spectral library tap73-mediated cell proliferation downstream effectors p-eif2α pentose phosphate pathway qrt-pcr primer sequences gamma-tocopherol induces apoptosis glucose-6-phosphate dehydrogenase anti-α-tubulin antibody social media complete media 50 µg/ml propidium iodide vital dye er-tracker reactive oxygen species original author research lymph node size thermo fisher scientific nadp+/nadph quantification kit permissions human disease mutations glyceraldehyde 3-phosphate dehydrogenase
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headline:A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo
description:Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here we demonstrate that the natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP. Polydatin blocks G6PD causing accumulation of reactive oxygen species and strong increase of endoplasmic reticulum stress. These effects are followed by cell cycle block in S phase, an about 50% of apoptosis, and 60% inhibition of invasion in vitro. Accordingly, in an orthotopic metastatic model of tongue cancer, 100âmg/kg polydatin induced an about 30% tumor size reduction with an about 80% inhibition of lymph node metastases and 50% reduction of lymph node size (pâ<â0.005). Polydatin is not toxic in animals up to a dose of 200âmg/kg and a phase II clinical trial shows that it is also well tolerated in humans (40âmg twice a day for 90 days). Thus, polydatin may be used as a reliable tool to limit human cancer growth and metastatic spread.
datePublished:2018-05-14T00:00:00Z
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headline:A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo
description:Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here we demonstrate that the natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP. Polydatin blocks G6PD causing accumulation of reactive oxygen species and strong increase of endoplasmic reticulum stress. These effects are followed by cell cycle block in S phase, an about 50% of apoptosis, and 60% inhibition of invasion in vitro. Accordingly, in an orthotopic metastatic model of tongue cancer, 100âmg/kg polydatin induced an about 30% tumor size reduction with an about 80% inhibition of lymph node metastases and 50% reduction of lymph node size (pâ<â0.005). Polydatin is not toxic in animals up to a dose of 200âmg/kg and a phase II clinical trial shows that it is also well tolerated in humans (40âmg twice a day for 90 days). Thus, polydatin may be used as a reliable tool to limit human cancer growth and metastatic spread.
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PostalAddress:
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Oncologia Medica ed Ematologia, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale âF. Magrassi e A. Lanzaraâ, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
name:The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
name:Department of Biochemistry, Biophysics and General Pathology, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Biochemistry, Biophysics and General Pathology, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Research, Pathology Unit, Istituto Nazionale Tumori- IRCCS- Fondazione Pascale, Naples, Italy
name:SSD Sperimentazione Animale, Istituto Nazionale Tumori- IRCCS- Fondazione Pascale, Naples, Italy
name:SSD Sperimentazione Animale, Istituto Nazionale Tumori- IRCCS- Fondazione Pascale, Naples, Italy
name:The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Biochemistry, Biophysics and General Pathology, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
name:Department of Experimental Medicine, University of Campania âLuigi Vanvitelliâ, Naples, Italy
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