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| The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring. Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate. Warburg effect (GLUT1, LDHA, HK2, and PKM2).Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export). Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) - HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: - PKM2 Inhibitors: (Shikonin) -Can reduce glycolysis - LDH Inhibitors: (Gossypol, FX11) -Reducing the conversion of pyruvate to lactate. -Inhibiting the production of ATP and NADH. - GLUT1 Inhibitors: (phloretin, WZB117) -A key transporter involved in glucose uptake. -GLUT3 Inhibitors: - PDK1 Inhibitors: (dichloroacetate) - A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure. 2.Pentose phosphate pathway: - G6PD Inhibitors: can reduce the pentose phosphate pathway 3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: - HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 4.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 5.mTOR pathway: - mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. Warburg Targeting Matrix (Cancer Metabolism)
Time-Scale Flag (TSF): P / R / G
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| 5273- | 3BP, | The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view |
| - | Review, | Var, | NA |
| 3453- | 5-ALA, | The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis |
| - | in-vitro, | Lung, | A549 |
| 2321- | ART/DHA, | Dihydroartemisinin mediating PKM2-caspase-8/3-GSDME axis for pyroptosis in esophageal squamous cell carcinoma |
| - | in-vitro, | ESCC, | Eca109 | - | in-vitro, | ESCC, | EC9706 |
| 2388- | Ash, | Withaferin A decreases glycolytic reprogramming in breast cancer |
| - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | BC, | MDA-MB-468 | - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-453 |
| 2707- | BBR, | Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway |
| - | in-vitro, | Liver, | HepG2 | - | in-vitro, | BC, | MCF-7 |
| 2710- | BBR, | Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells |
| - | in-vitro, | Ovarian, | SKOV3 |
| 2347- | CAP, | Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis |
| - | in-vivo, | Nor, | NA | - | in-vitro, | Nor, | RAW264.7 |
| 2348- | CAP, | Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry |
| - | Analysis, | Nor, | NA |
| 2393- | Cela, | Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect |
| - | in-vivo, | Sepsis, | NA | - | in-vitro, | Nor, | RAW264.7 |
| 2392- | Cela, | The role of natural products targeting macrophage polarization in sepsis-induced lung injury |
| - | Review, | Sepsis, | NA |
| 1583- | Citrate, | Extracellular citrate and metabolic adaptations of cancer cells |
| - | Review, | NA, | NA |
| 2307- | CUR, | Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin |
| - | in-vitro, | Colon, | HT29 | - | in-vitro, | Laryn, | FaDu |
| 1875- | DCA, | Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells |
| - | in-vitro, | neuroblastoma, | NA | - | in-vivo, | NA, | NA |
| 1884- | DCA, | Sal, | Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines |
| - | in-vitro, | CRC, | DLD1 | - | in-vitro, | CRC, | HCT116 |
| 1873- | DCA, | Dual-targeting of aberrant glucose metabolism in glioblastoma |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | U251 |
| 2352- | dietFMD, | Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines |
| - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | BC, | MCF-7 |
| 1863- | dietFMD, | Chemo, | Effect of fasting on cancer: A narrative review of scientific evidence |
| - | Review, | Var, | NA |
| 1861- | dietFMD, | Chemo, | Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models |
| - | in-vitro, | Colon, | CT26 | - | in-vivo, | NA, | NA |
| 5069- | dietSTF, | The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases |
| - | Review, | Var, | NA |
| 649- | EGCG, | CUR, | PI, | Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets |
| - | Review, | Var, | NA |
| 2313- | Flav, | Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism |
| - | Review, | Var, | NA |
| 2545- | M-Blu, | Reversing the Warburg Effect as a Treatment for Glioblastoma |
| - | in-vitro, | GBM, | U87MG | - | NA, | AD, | NA | - | in-vitro, | GBM, | A172 | - | in-vitro, | GBM, | T98G |
| 2542- | M-Blu, | In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death |
| - | in-vitro, | Ovarian, | OV1369 | - | in-vitro, | Ovarian, | OV1946 | - | in-vitro, | Nor, | ARPE-19 |
| 2540- | M-Blu, | Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 1782- | MEL, | Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities |
| - | Review, | Var, | NA |
| 994- | MET, | Tumor metabolism destruction via metformin-based glycolysis inhibition and glucose oxidase-mediated glucose deprivation for enhanced cancer therapy |
| - | in-vitro, | Var, | NA |
| 2377- | MET, | Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells |
| - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Cerv, | SiHa |
| 2245- | MF, | Quantum based effects of therapeutic nuclear magnetic resonance persistently reduce glycolysis |
| - | in-vitro, | Nor, | NIH-3T3 |
| 5254- | NCL, | The magic bullet: Niclosamide |
| - | Review, | Var, | NA |
| 2332- | RES, | Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism |
| - | Review, | Var, | NA |
| 2441- | RES, | Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions |
| - | Review, | Var, | NA |
| 1748- | RosA, | The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity |
| - | Review, | Var, | NA |
| 3006- | RosA, | Rosmarinic acid attenuates glioblastoma cells and spheroids’ growth and EMT/stem-like state by PTEN/PI3K/AKT downregulation and ERK-induced apoptosis |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | LN229 |
| 3003- | RosA, | Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3001- | RosA, | Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review |
| - | Review, | Var, | NA |
| 3036- | RosA, | Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells |
| - | in-vitro, | CRC, | HCT8 | - | in-vitro, | CRC, | HCT116 | - | in-vitro, | CRC, | LS174T |
| 2403- | SFN, | Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane |
| - | in-vitro, | Pca, | LNCaP | - | in-vitro, | Pca, | 22Rv1 | - | in-vitro, | Pca, | PC3 | - | in-vivo, | NA, | NA |
| 2417- | SK, | Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H446 |
| 2356- | SK, | ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment |
| - | in-vitro, | Ovarian, | CaOV3 | - | in-vitro, | Ovarian, | OV90 | - | in-vivo, | NA, | NA |
| 2185- | SK, | Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis |
| - | in-vitro, | Lung, | LLC1 | - | in-vitro, | Melanoma, | B16-BL6 | - | in-vivo, | NA, | NA |
| 3425- | TQ, | Advances in research on the relationship between thymoquinone and pancreatic cancer |
| 3431- | TQ, | PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | CRC, | SW48 |
| 4846- | Uro, | Urolithin A exerts anti-tumor effects on gastric cancer via activating autophagy-Hippo axis and modulating the gut microbiota |
| - | in-vivo, | GC, | NA |
| 3136- | VitC, | Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer |
| - | in-vitro, | Colon, | SW48 | - | in-vitro, | Colon, | LoVo |
| 3138- | VitC, | The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity |
| - | in-vitro, | RCC, | RCC4 | - | in-vitro, | CRC, | HCT116 | - | in-vitro, | BC, | MDA-MB-435 | - | in-vitro, | Ovarian, | SKOV3 | - | in-vitro, | Colon, | SW48 | - | in-vitro, | GBM, | U251 |
| 3140- | VitC, | Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest |
| - | in-vitro, | PC, | MIA PaCa-2 | - | in-vitro, | Nor, | HEK293 |
| 3137- | VitC, | Vitamin C inhibits the growth of colorectal cancer cell HCT116 and reverses the glucose-induced oncogenic effect by downregulating the Warburg effect |
| - | in-vitro, | CRC, | HCT116 |
| 3141- | VitC, | High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer |
| - | in-vitro, | CRC, | HCT116 |
| 3145- | VitC, | Warburg_effect">Vitamin C inhibits the growth of colorectal cancer cell HCT116 and reverses the glucose‐induced oncogenic effect by downregulating the Warburg effect |
| - | in-vitro, | CRC, | HCT116 |
| 2367- | VitD3, | Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia |
| - | in-vivo, | AML, | NA |
| 2365- | VitD3, | Vitamin D Affects the Warburg Effect and Stemness Maintenance of Non- Small-Cell Lung Cancer Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H1975 | - | in-vivo, | NA, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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