| 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 |
| 2332- | RES, | Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism |
| - | Review, | Var, | NA |
| 2331- | RES, | Resveratrol improves follicular development of PCOS rats via regulating glycolysis pathway and targeting SIRT1 |
| - | in-vivo, | Nor, | NA |
| 2330- | RES, | Resveratrol Induces Cancer Cell Apoptosis through MiR-326/PKM2-Mediated ER Stress and Mitochondrial Fission |
| - | in-vitro, | CRC, | DLD1 | - | in-vitro, | Cerv, | HeLa | - | in-vitro, | BC, | MCF-7 |
| 2329- | RES, | Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis |
| - | in-vitro, | Melanoma, | A375 |
| 2328- | RES, | Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin |
| - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Liver, | HepG2 | - | in-vitro, | BC, | MCF-7 |
| 2439- | RES, | By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice |
| - | in-vitro, | HCC, | HCCLM3 | - | in-vitro, | Nor, | L02 | - | in-vitro, | HCC, | SMMC-7721 cell | - | in-vitro, | HCC, | Bel-7402 | - | in-vitro, | HCC, | HUH7 |
| 2404- | SFN, | Prostate cancer chemoprevention by sulforaphane in a preclinical mouse model is associated with inhibition of fatty acid metabolism |
| - | in-vitro, | Pca, | LNCaP | - | in-vitro, | Pca, | 22Rv1 | - | in-vivo, | NA, | NA |
| 2405- | SFN, | Sulforaphane Targets the TBX15/KIF2C Pathway to Repress Glycolysis and Cell Proliferation in Gastric Carcinoma Cells |
| - | in-vitro, | GC, | SGC-7901 | - | in-vitro, | GC, | BGC-823 |
| 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 |
| 2406- | SFN, | Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach |
| - | Review, | Pca, | NA |
| 2445- | SFN, | Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | BC, | SkBr3 |
| 2306- | SIL, | CUR, | RES, | EA, | Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment |
| - | in-vitro, | BC, | MDA-MB-231 |
| 2410- | SIL, | Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | U251 | - | in-vivo, | NA, | NA |
| 2359- | SK, | Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery |
| - | in-vivo, | Liver, | NA |
| 2420- | SK, | Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury |
| - | in-vivo, | AKI, | NA |
| 2419- | SK, | Regulation of glycolysis and the Warburg effect in wound healing |
| - | in-vivo, | Nor, | NA |
| 2418- | SK, | Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin Through Regulating PKM2 |
| - | in-vitro, | HCC, | SMMC-7721 cell | - | in-vitro, | HCC, | HUH7 | - | in-vitro, | HCC, | HepG2 |
| 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 |
| 2416- | SK, | Shikonin induces cell death by inhibiting glycolysis in human testicular cancer I-10 and seminoma TCAM-2 cells |
| - | in-vitro, | Testi, | TCAM-2 |
| 2415- | SK, | Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways |
| - | in-vivo, | Arthritis, | NA |
| 2354- | SK, | PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation |
| - | in-vivo, | Sepsis, | NA |
| 2355- | SK, | Pharmacological properties and derivatives of shikonin-A review in recent years |
| - | Review, | Var, | NA |
| 2370- | SK, | The role of pyruvate kinase M2 in anticancer therapeutic treatments |
| - | Review, | Var, | NA |
| 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 |
| 2357- | SK, | GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism |
| - | Study, | HCC, | NA | - | in-vivo, | NA, | NA |
| 2358- | SK, | SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2 |
| - | in-vivo, | Park, | NA |
| 2360- | SK, | Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathway |
| - | in-vitro, | NPC, | HONE1 | - | in-vitro, | NPC, | SUNE-1 |
| 2361- | SK, | Natural shikonin and acetyl-shikonin improve intestinal microbial and protein composition to alleviate colitis-associated colorectal cancer |
| - | in-vivo, | CRC, | NA |
| 2362- | SK, | RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide |
| - | in-vitro, | GBM, | U87MG | - | in-vivo, | GBM, | NA | - | in-vitro, | GBM, | U251 |
| 2363- | SK, | Inhibition of PKM2 by shikonin impedes TGF-β1 expression by repressing histone lactylation to alleviate renal fibrosis |
| - | in-vivo, | CKD, | NA |
| 2364- | SK, | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
| - | in-vivo, | PSA, | NA |
| 2191- | SK, | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
| - | in-vitro, | Melanoma, | NA |
| 2200- | SK, | Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis |
| - | in-vitro, | Thyroid, | CAL-62 | - | in-vitro, | Thyroid, | 8505C |
| 2197- | SK, | Shikonin derivatives for cancer prevention and therapy |
| - | Review, | Var, | NA |
| 2196- | SK, | Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species |
| - | Review, | Var, | NA |
| 2194- | SK, | Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo |
| - | in-vitro, | ESCC, | Eca109 | - | in-vitro, | ESCC, | EC9706 | - | in-vivo, | NA, | NA |
| 2192- | SK, | Shikonin Inhibits Tumor Growth of ESCC by suppressing PKM2 mediated Aerobic Glycolysis and STAT3 Phosphorylation |
| - | in-vitro, | ESCC, | KYSE-510 | - | in-vitro, | ESCC, | Eca109 | - | in-vivo, | NA, | NA |
| 2190- | SK, | Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway |
| - | in-vitro, | HCC, | HCCLM3 |
| 2189- | SK, | PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells |
| - | in-vitro, | Melanoma, | NA |
| 2187- | SK, | VitK3, | Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells |
| - | in-vitro, | BC, | MCF-7 |
| 2186- | SK, | Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line |
| - | in-vitro, | HCC, | HepG2 | - | in-vitro, | HCC, | HCCLM3 |
| 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 |
| 2184- | SK, | Cisplatin, | PKM2 Inhibitor Shikonin Overcomes the Cisplatin Resistance in Bladder Cancer by Inducing Necroptosis |
| - | in-vitro, | CRC, | T24/HTB-9 |
| 2182- | SK, | Cisplatin, | Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | PC9 | - | in-vivo, | NA, | NA |
| 2181- | SK, | Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2 |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | Lung, | A549 | - | in-vitro, | Cerv, | HeLa |
| 2223- | SK, | Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review |
| - | in-vitro, | Var, | NA |
| 3045- | SK, | Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2) |
| - | in-vitro, | PC, | MIA PaCa-2 |
| 3041- | SK, | Promising Nanomedicines of Shikonin for Cancer Therapy |
| - | Review, | Var, | NA |
| 3040- | SK, | Pharmacological Properties of Shikonin – A Review of Literature since 2002 |
| - | Review, | Var, | NA | - | Review, | IBD, | NA | - | Review, | Stroke, | NA |
| 2470- | SK, | PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism |
| - | in-vitro, | Lung, | H1299 |
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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