ArticleInternational journal of molecular sciences2019
Curcumin Treatment in Combination with Glucose Restriction Inhibits Intracellular Alkalinization and Tumor Growth in Hepatoma Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial.Nutrition & diabetes · 2024Trial
- Exosome-like nanoparticles derived fromInternational journal of pharmaceutics: X · 2026Article
- Inhibition of NHE1 Overcomes Temozolomide-Resistance in Glioblastoma via ROS-AKT/ERK Axis-Mediated Autophagy Suppression.Journal of biochemical and molecular toxicology · 2026Article
- Natural Products in Cancer Prevention and Therapy: Current Challenges and Future Directions.MedComm · 2026Review
- Review
- YULINK deficiency promotes cell death under glucose restriction in HCC cells in association with GLUT1-mediated glycolysis.Molecular medicine (Cambridge, Mass.) · 2025Article
- A novel approach to regulate glucose uptake in an anaplastic thyroid cancer cell line.Endocrine connections · 2025Article
- Role of Curcumin in Chronic Liver Diseases: A Comprehensive Review.Drug design, development and therapy · 2025Review
- HKDC1 functions as a glucose sensor and promotes metabolic adaptation and cancer growth via interaction with PHB2.Cell death and differentiation · 2024Article
- Impact of Caloric Restriction in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Prospective Case Control Study.Nutrients · 2023Article
- Effects of Obesity and Calorie Restriction on Cancer Development.International journal of molecular sciences · 2023Review
- Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future.Pharmaceutics · 2023Review
- Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation.Cancer cell international · 2022Article
- Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse.Cancers · 2022Article
- Advances in research on the regulatory mechanism of NHE1 in tumors.Oncology letters · 2021Review
- Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ.Journal of cellular and molecular medicine · 2020Article
- Pathophysiology of hepatic NaExperimental and therapeutic medicine · 2020Review
- Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy.International journal of molecular sciences · 2019Review
- Phytochemicals as Modulators of Long Non-Coding RNAs and Inhibitors of Cancer-Related Carbonic Anhydrases.International journal of molecular sciences · 2019Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein-protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GβL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.
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Registered trials
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