ArticleMedical oncology (Northwood, London, England)2023
Novel phloretin-based combinations targeting glucose metabolism in hepatocellular carcinoma through GLUT2/PEPCK axis of action: in silico molecular modelling and in vivo studies.
Article in Medical oncology (Northwood, London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 12 citations in OpenAlex.
- Development of Type II Glucose Transporter Inhibitors: Phloretin as a GLUT-2 Screening Template fromBiomedicines · 2026Article
- Vitamin B17 alleviates Sorafenib-induced cardiotoxicity in Ehrlich Ascites Carcinoma mice via modulation of inflammatory and fibrotic pathways.Scientific reports · 2025Article
- USP6NL knockdown suppresses colorectal cancer progression by inducing CASP9-Mediated apoptosis and disrupting FOXC2/SNAI1-Driven EMT and angiogenesis.Functional & integrative genomics · 2025Article
- Gold nanoparticles mediate suppression of angiogenesis and breast cancer growth via MMP-9/NF-κB/mTOR and PD-L1/PD-1 signaling: integrative in vitro validation and network pharmacology insights.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Combination treatment with Phloretin enhances the anti-tumor efficacy of radiotherapy in lung cancer models.Discover oncology · 2025Article
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- Probiotic-derived silver nanoparticles target mTOR/MMP-9/BCL-2/dependent AMPK activation for hepatic cancer treatment.Medical oncology (Northwood, London, England) · 2024Article
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7 authors at 2 institutions in 1 country.
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Abstract
Hepatocellular carcinoma (HCC) is commonly associated with disturbances in glucose metabolism and enhanced glycolysis. However, a controversial role for gluconeogenesis was reported to be tumor-promoting and tumor-suppressive. We investigated novel anti-HCC treatments through either the simultaneous inhibition of glycolysis and gluconeogenesis by "phloretin" and "sodium meta-arsenite", respectively (Combination 1); or the concurrent inhibition of glycolysis and induction of gluconeogenesis by phloretin and dexamethasone, respectively, (combination 2). A total of 110 Swiss albino mice were divided into eleven groups, HCC was induced by N, N-dimethyl-4-aminoazobenzene. We have measured the expression of the glucose transporter 2 (GLUT2), Phosphoenolpyruvate carboxykinases (PEPCK), Caspase-3, Beclin 1, Cyclin D1, and cytokeratin 18 genes; blood glucose and ATP levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Furthermore, in silico molecular docking was performed to investigate the potential drug-receptor interactions. Histologically, the phloretin-based combinations resulted in a significant regression of malignant tissue compared to various treatments. GLUT2 and PEPCK mRNA analysis indicated successful off/on modulation of glycolysis and gluconeogenesis. Docking confirmed the potent binding between phloretin, sodium meta-arsenite, and dexamethasone with GLUT2, PEPCK, and Retinoid X Receptor Alpha, respectively. Molecularly, Combination 2 resulted in the highest reduction in cyclin D1, cytokeratin 18, and Beclin 1 expression contemporaneously with the upregulation in Caspase-3 levels. Biochemically, both combinations caused a significant reduction in ATP levels, ALT, and AST activity compared to the other groups. In conclusion, we propose two novel phloretin-based combinations that can be used in treating HCC through the regulation of glucose metabolism and ATP production.
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