| Source: |
| Type: enzyme |
| PKM2 (Pyruvate Kinase, Muscle 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PKM2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells. -C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A -PKM2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells. -inhibition of PKM2 may cause ATP depletion and inhibiting glycolysis. -PK exists in four isoforms: PKM1, PKM2, PKR, and PKL -PKM2 plays a role in the regulation of glucose metabolism in diabetes. -PKM2 is involved in the regulation of cell proliferation, apoptosis, and autophagy. – Pyruvate kinase catalyzes the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate with the production of ATP. – The PKM2 isoform is uniquely regulated and can exist in both highly active tetrameric and less active dimeric forms. – Cancer cells often favor the dimeric form of PKM2 to slow pyruvate production, thereby accumulating upstream glycolytic intermediates that can be diverted into anabolic pathways to support cell growth and proliferation. – Under low oxygen conditions, cancer cells rely on altered metabolic pathways in which PKM2 is a key player. – The shift to aerobic glycolysis (Warburg effect) orchestrated in part by PKM2 helps tumor cells survive and grow in hypoxic conditions. – Elevated expression of PKM2 is frequently observed in many cancer types, including lung, breast, colorectal, and pancreatic cancers. – High levels of PKM2 are often correlated with enhanced tumor aggressiveness, poor differentiation, and advanced clinical stage. PKM2 in carcinogenesis and oncotherapy Inhibitors of PKM2: -Shikonin, Resveratrol, Baicalein, EGCG, Apigenin, Curcumin, Ursolic Acid, Citrate (best known as an allosteric inhibitor of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis) potential to directly inhibit or modulate PKM2 is less well established Full List of PKM2 inhibitors from Database -key connected observations: Glycolysis↓, lactateProd↓, ROS↑ in cancer cell, while some result for opposite effect on normal cells. Tumor pyruvate kinase M2 modulators Flavonoids effect on PKM2 Compounds name IC50/AC50uM Effect Flavonols 1. Fisetin 0.90uM Inhibition 2. Rutin 7.80uM Inhibition 3. Galangin 8.27uM Inhibition 4. Quercetin 9.24uM Inhibition 5. Kaempferol 9.88uM Inhibition 6. Morin hydrate 37.20uM Inhibition 7. Myricetin 0.51uM Activation 8. Quercetin 3-b- D-glucoside 1.34uM Activation 9. Quercetin 3-D -galactoside 27-107uM Ineffective Flavanons 10. Neoeriocitrin 0.65uM Inhibition 11. Neohesperidin 14.20uM Inhibition 12. Naringin 16.60uM Inhibition 13. Hesperidin 17.30uM Inhibition 14. Hesperitin 29.10uM Inhibition 15. Naringenin 70.80uM Activation Flavanonols 16. (-)-Catechin gallateuM 0.85 Inhibition 17. (±)-Taxifolin 1.16uM Inhibition 18. (-)-Epicatechin 1.33uM Inhibition 19. (+)-Gallocatechin 4-16uM Ineffective Phenolic acids 20. Ferulic 11.4uM Inhibition 21. Syringic and 13.8uM Inhibition 22. Caffeic acid 36.3uM Inhibition 23. 3,4-Dihydroxybenzoic acid 78.7uM Inhibition 24. Gallic acid 332.6uM Inhibition 25. Shikimic acid 990uM Inhibition 26. p-Coumaric acid 22.2uM Activation 27. Sinapinic acids 26.2uM Activation 28. Vanillic 607.9uM Activation |
| 2395- | EGCG, | EGCG inhibits diabetic nephrophathy through up regulation of PKM2 |
| - | Study, | Diabetic, | NA |
| 2302- | EGCG, | Flavonoids Targeting HIF-1: Implications on Cancer Metabolism |
| - | Review, | Var, | NA |
| 2309- | EGCG, | Chemo, | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
| - | in-vitro, | PC, | MIA PaCa-2 | - | in-vitro, | Nor, | HPNE | - | in-vitro, | PC, | PANC1 | - | in-vivo, | NA, | NA |
| 2422- | EMD, | Anti-Cancer Effects of Emodin on HepG2 Cells as Revealed by 1H NMR Based Metabolic Profiling |
| - | in-vitro, | HCC, | HepG2 |
| 2345- | EMD, | Emodin ameliorates antioxidant capacity and exerts neuroprotective effect via PKM2-mediated Nrf2 transactivation |
| - | in-vitro, | AD, | PC12 |
| 1654- | FA, | Molecular mechanism of ferulic acid and its derivatives in tumor progression |
| - | Review, | Var, | NA |
| 2401- | Flav, | In vitro effects of some flavonoids and phenolic acids on human pyruvate kinase isoenzyme M2 |
| - | in-vitro, | Nor, | 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 |
| 2400- | HCAs, | The Mixture of Ferulic Acid and P-Coumaric Acid Suppresses Colorectal Cancer through lncRNA 495810/PKM2 Mediated Aerobic Glycolysis |
| - | in-vitro, | CRC, | NA | - | in-vivo, | CRC, | NA |
| 2407- | HCAs, | 2'-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2 |
| - | in-vitro, | Pca, | DU145 | - | in-vitro, | Pca, | LNCaP |
| 2178- | itraC, | Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer |
| - | in-vivo, | CRC, | HCT116 |
| 2390- | KaempF, | Kaempferol Can Reverse the 5-Fu Resistance of Colorectal Cancer Cells by Inhibiting PKM2-Mediated Glycolysis |
| - | in-vitro, | CRC, | HCT8 |
| 2351- | lamb, | Anti-Warburg effect via generation of ROS and inhibition of PKM2/β-catenin mediates apoptosis of lambertianic acid in prostate cancer cells |
| - | in-vitro, | Pca, | DU145 | - | in-vitro, | Pca, | PC3 |
| 2346- | LT, | Luteolin suppressed PKM2 and promoted autophagy for inducing the apoptosis of hepatocellular carcinoma cells |
| - | in-vitro, | HCC, | HepG2 |
| 2376- | MET, | Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway |
| - | in-vitro, | Nor, | NA |
| 2375- | MET, | Metformin inhibits gastric cancer via the inhibition of HIF1α/PKM2 signaling |
| - | in-vitro, | GC, | SGC-7901 |
| 2371- | MET, | The role of pyruvate kinase M2 in anticancer therapeutic treatments |
| - | Review, | 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 |
| 2378- | MET, | Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1α/PKM2/STAT3 pathway |
| - | in-vitro, | SCC, | CAL27 | - | in-vivo, | NA, | NA |
| 2379- | MET, | Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer |
| - | in-vitro, | Bladder, | T24/HTB-9 | - | in-vitro, | BC, | UMUC3 |
| 2374- | MET, | Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | SkBr3 | - | in-vitro, | BC, | MDA-MB-231 |
| 2384- | MET, | Integration of metabolomics and transcriptomics reveals metformin suppresses thyroid cancer progression via inhibiting glycolysis and restraining DNA replication |
| - | in-vitro, | Thyroid, | BCPAP | - | in-vivo, | NA, | NA | - | in-vitro, | Thyroid, | TPC-1 |
| 2385- | MET, | Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model |
| - | in-vitro, | AD, | H4 | - | in-vitro, | NA, | HEK293 | - | in-vivo, | NA, | NA | - | in-vitro, | NA, | SH-SY5Y |
| 2386- | MET, | Mechanisms of metformin inhibiting cancer invasion and migration |
| - | Review, | Var, | NA |
| 2387- | MET, | GEM, | Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis |
| - | in-vitro, | CCA, | HCC9810 |
| 2249- | MF, | Pulsed electromagnetic fields modulate energy metabolism during wound healing process: an in vitro model study |
| - | in-vitro, | Nor, | L929 |
| 2260- | MF, | Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | LN229 | - | in-vivo, | NA, | NA |
| 525- | MF, | Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis |
| - | in-vitro, | Nor, | HUVECs |
| 991- | OA, | Blockade of glycolysis-dependent contraction by oroxylin a via inhibition of lactate dehydrogenase-a in hepatic stellate cells |
| - | in-vivo, | NA, | NA | - | in-vivo, | Nor, | NA |
| 2452- | PA, | Targeting Pyruvate Kinase M2 and Hexokinase II, Pachymic Acid Impairs Glucose Metabolism and Induces Mitochondrial Apoptosis |
| - | in-vitro, | BC, | SkBr3 |
| 2396- | PACs, | PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma |
| - | in-vitro, | HCC, | HCCLM3 | - | in-vitro, | HCC, | SMMC-7721 cell | - | in-vitro, | HCC, | Bel-7402 | - | in-vitro, | HCC, | HUH7 | - | in-vitro, | HCC, | HepG2 | - | in-vitro, | Nor, | L02 |
| 2429- | PB, | Impact of butyrate on PKM2 and HSP90β expression in human colon tissues of different transformation stages: a comparison of gene and protein data |
| - | in-vitro, | Colon, | NA |
| 1231- | PBG, | Caffeic acid phenethyl ester inhibits MDA-MB-231 cell proliferation in inflammatory microenvironment by suppressing glycolysis and lipid metabolism |
| - | in-vitro, | BC, | MDA-MB-231 |
| 1672- | PBG, | The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers |
| - | Review, | BC, | NA |
| 1661- | PBG, | Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways |
| - | Review, | Var, | NA |
| 1664- | PBG, | Anticancer Activity of Propolis and Its Compounds |
| - | Review, | Var, | NA |
| - | in-vitro, | HCC, | HepG2 |
| 2381- | PBG, | Chinese Poplar Propolis Inhibits MDA-MB-231 Cell Proliferation in an Inflammatory Microenvironment by Targeting Enzymes of the Glycolytic Pathway |
| - | in-vitro, | BC, | MDA-MB-231 |
| 2380- | PBG, | Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy |
| - | Review, | Var, | NA |
| 2409- | PTS, | Pterostilbene Induces Pyroptosis in Breast Cancer Cells through Pyruvate Kinase 2/Caspase-8/Gasdermin C Signaling Pathway |
| - | in-vitro, | BC, | EMT6 | - | in-vitro, | BC, | 4T1 | - | in-vitro, | Nor, | HC11 |
| 2408- | PTS, | Pterostilbene suppresses the growth of esophageal squamous cell carcinoma by inhibiting glycolysis and PKM2/STAT3/c-MYC signaling pathway |
| - | in-vitro, | ESCC, | NA |
| 2343- | QC, | Pharmacological Activity of Quercetin: An Updated Review |
| - | Review, | Nor, | NA |
| 2338- | QC, | Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury |
| - | Review, | Nor, | NA |
| 2339- | QC, | Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation |
| - | in-vivo, | Nor, | NA |
| 2340- | QC, | Oral Squamous Cell Carcinoma Cells with Acquired Resistance to Erlotinib Are Sensitive to Anti-Cancer Effect of Quercetin via Pyruvate Kinase M2 (PKM2) |
| - | in-vitro, | OS, | NA |
| 2341- | QC, | Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-231 | - | in-vivo, | NA, | NA |
| 2344- | QC, | Quercetin: A natural solution with the potential to combat liver fibrosis |
| - | Review, | Nor, | NA |
| 910- | QC, | The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism |
| 2333- | RES, | Resveratrol regulates insulin resistance to improve the glycolytic pathway by activating SIRT2 in PCOS granulosa cells |
| - | in-vitro, | Nor, | NA |
| 2334- | RES, | Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy |
| - | Review, | Var, | 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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:% Target#:772 State#:% Dir#:%
wNotes=0 sortOrder:rid,rpid