| 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 |
| Cyclooxygenase (COX)-2 overexpression has been noted in various cancers.
PI3Ks/AKT pathways are over-activated in several types of cancers. EGFR altered activity has been noted in various pathological conditions. However, its regulation is an important step in the inhibition of cancer. In this regard, EGCG shows a pivotal role in the inhibition of EGFR activity. Activating protein-1 transcription factor has been associated with pathogenesis including cancer. Activation of the sonic hedgehog (Shh) pathway is required for the growth of numerous tissues and organs and recent evidence indicates that this pathway is often recruited to stimulate growth of cancer stem cells (CSCs) and to orchestrate the reprogramming of cancer cells via epithelial mesenchymal transition (EMT). Increased expression of Nanog has been associated with the aggressive nature of certain cancers, highlighting its role in promoting cancer stem cell characteristics. The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. The process of cell apoptosis is often accompanied by the destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses50. Several studies have demonstrated that high cyclin D1 expression was observed in cancers including breast, lung, prostate, lymph node and colorectal cancers [23–25]. The oncogene c-myc, which is frequently over-expressed in cancer cells, is involved in the transactivation of most of the glycolytic enzymes including lactate dehydrogenase A (LDHA) and the glucose transporter GLUT1 [51,52]. Thus, c-myc activation is a likely candidate to promote the enhanced glucose uptake and lactate release in the proliferating cancer cell. Vimentin is overexpressed in various epithelial cancers, including prostate cancer, gastrointestinal tumors, tumors of the central nervous system, breast cancer, malignant melanoma, and lung cancer. Vimentin’s overexpression in cancer correlates well with accelerated tumor growth, invasion, and poor prognosis; however, the role of vimentin in cancer progression remains obscure. Heat shock proteins (HSPs) are normally induced under environmental stress to serve as chaperones for maintenance of correct protein folding but they are often overexpressed in many cancers, including breast cancer. Since NQO1 is highly expressed in many solid tumors, including via upregulation of Nrf2, the design of compounds activated by NQO1 and NQO1-targeted drug delivery have been active areas of research. Since increased Nrf2 gene expression is one of the main mechanisms of cancer cells in resisting chemotherapeutic drugs and survival in oxidative conditions; finding compounds with the ability to suppress Nrf2 gene expression with minimum side effects can be considered an important strategy for increasing the sensitivity of cancer cells to chemotherapy. Overexpression of c-met stimulates proliferation, migration and invasion in various types of cancer including prostate cancer. Overexpression of TGFα and EGFR by many carcinomas correlates with the development of cancer metastasis, resistance to chemotherapy and poor prognosis. More than 50% of human cancers have a mutated nonfunctional p53. |
| 2325- | 2DG, | Research Progress of Warburg Effect in Hepatocellular Carcinoma |
| - | Review, | Var, | NA |
| 2299- | Api, | Flavonoids Targeting HIF-1: Implications on Cancer Metabolism |
| - | Review, | Var, | NA |
| 3383- | ART/DHA, | Dihydroartemisinin: A Potential Natural Anticancer Drug |
| - | Review, | Var, | NA |
| 2324- | ART/DHA, | Research Progress of Warburg Effect in Hepatocellular Carcinoma |
| - | Review, | Var, | NA |
| 2297- | Ba, | Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells – A potential contribution to the predictive, preventive, and personalized medicine |
| - | Review, | Var, | NA |
| 1576- | Citrate, | Targeting citrate as a novel therapeutic strategy in cancer treatment |
| - | Review, | Var, | NA |
| 2312- | CUR, | Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy |
| - | Review, | Var, | NA |
| 2302- | EGCG, | Flavonoids Targeting HIF-1: Implications on Cancer Metabolism |
| - | Review, | Var, | NA |
| 1654- | FA, | Molecular mechanism of ferulic acid and its derivatives in tumor progression |
| - | 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 |
| 2371- | MET, | The role of pyruvate kinase M2 in anticancer therapeutic treatments |
| - | Review, | Var, | NA |
| 2386- | MET, | Mechanisms of metformin inhibiting cancer invasion and migration |
| - | Review, | Var, | 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 |
| 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 |
| 2334- | RES, | Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy |
| - | Review, | Var, | NA |
| 2332- | RES, | Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism |
| - | Review, | Var, | 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 |
| 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 |
| 2223- | SK, | Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review |
| - | in-vitro, | Var, | NA |
| 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 |
| 2373- | TMZ, | The role of pyruvate kinase M2 in anticancer therapeutic treatments |
| - | Review, | Var, | NA |
| 2411- | UA, | Ursolic acid in health and disease |
| - | Review, | Var, | NA |
| 2428- | VitK3, | Vitamin K3 and K5 are inhibitors of tumor pyruvate kinase M2 |
| - | Study, | Var, | NA |
| 2372- | VitK3, | The role of pyruvate kinase M2 in anticancer therapeutic treatments |
| - | Review, | Var, | NA |
| 2397- | Wor, | Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action |
| - | 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
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