| Features: treatment category |
| Chemotherapy is a treatment approach that uses drugs to target and kill rapidly dividing cells, primarily cancer cells. However, because many normal cells also divide quickly (such as those in the bone marrow, digestive tract, and hair follicles), chemotherapy can also affect these cells, leading to a range of side effects. Main Classes of Chemotherapy Agents and Examples Alkylating Agents: -work by adding alkyl groups to DNA, which interferes with the DNA’s structure and prevents replication. Examples: Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil, Busulfan. Anti-metabolites: -interfere with DNA and RNA synthesis by substituting for the normal building blocks of nucleic acids. Examples: Methotrexate, 5-Fluorouracil (5-FU), Cytarabine, Gemcitabine, 6-Mercaptopurine. Anti-microtubule Agents: -interfere with the structures that separate chromosomes during cell division (mitosis). Examples: Paclitaxel, Docetaxel, Vincristine, Vinblastine. Topoisomerase Inhibitors: -target the enzymes topoisomerase I and II, which control the changes in DNA structure required for replication. Examples: Etoposide (topoisomerase II inhibitor), Irinotecan (topoisomerase I inhibitor), Topotecan. Cytotoxic Antibiotics: -intercalate into DNA, inhibiting the replication of cancer cells. Examples: Doxorubicin, Daunorubicin, Bleomycin, Mitoxantrone. Platinum-Based Agents: -contain platinum and cause cross-linking of DNA, which interferes with DNA repair and replication. Examples: Cisplatin, Carboplatin, Oxaliplatin. Many chemotherapy agents exert their effects, at least in part, by inducing oxidative stress in cancer cells. They can increase ROS levels through several mechanisms: -Direct generation of free radicals. -Disruption of mitochondrial function, leading to increased production of ROS. -Interference with the cell’s antioxidant systems. -May want to avoid antioxidants 7 days bef ore and 7 days after chemo. Examples: NAC, Glutathione, Alpha Lipoic Acid, Vitamin E -anti-oxidants known to have pro-oxidant effects (like Quercetin, Curcumin, etc.) should not be taken 2-3 days before and after chemo -pro-oxidants known to bring good benefit to chemo can be continued during chemo. Examples are: Omega 3, Aremisia Annua, Silver NanoParticles. |
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| 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 |
| 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 |
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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