| Features: Promote calcium and phosphorus absorption | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Vitamin D3 (Cholecalciferol) - Major VITAL study stated Vit D did not reduce invasive cancer, but Secondary Analysis stated reduces the incidence of metastatic cancer at diagnosis. - Amount needed may depend on your BMI. - Vitamin D deficiency, as determined by serum 25(OH)D concentrations of less than 30 ng/mL, - Target achieving 80 ng/mL - Vitamin D may modulate oxidative stress markers. (ROS) - Nrf2 plays a key role in protecting cells against oxidative stress; this is modulated by vitamin D - Vitamin D has antioxidant and anti-inflammatory regulatory effects; whether supplementation alters response to specific chemotherapy regimens remains context-dependent and not firmly established. - excess Vit D can raise calcium and cause harm Vitamin D deficiency is generally defined as serum 25(OH)D <20 ng/mL (50 nmol/L), though some guidelines consider ≥30 ng/mL sufficient. - One recommendation is to get your level up to around 125 ng/ml (however not supported by consensus clinical trial evidence). - Chemo depletes Vitamin D levels so 10,000 IUs daily? – ask your doctor first. Typical maintenance dosing for most adults is 800–2000 IU/day; higher doses may be used short-term under medical supervision when correcting deficiency. After correction of vitamin D deficiency through loading doses of oral vitamin D (or safe sun exposure), adequate maintenance doses of vitamin D3 are needed. This can be achieved in approximately 90% of the adult population with vitamin D supplementation between 1000 to 4000 IU/day, 10,000 IU twice a week, or 50,000 IU twice a month [10,125]. On a population basis, such doses would allow approximately 97% of people to maintain their serum 25(OH)D concentrations above 30 ng/mL [19,126]. Others, such as persons with obesity, those with gastrointestinal disorders, and during pregnancy and lactation, are likely to require doses of 6,000 IU/day. Vitamin D, particularly its active form 1,25-dihydroxyvitamin D (calcitriol), exerts multiple biological effects that may influence cancer development and progression. Calcitriol has been reported to induce cell cycle arrest (often at the G0/G1 phase) and promote pro-apoptotic mechanisms in various cancer cell types. Inhibition of Angiogenesis: Some studies indicate that vitamin D can reduce the expression of pro-angiogenic factors, thereby potentially limiting the blood supply to tumors, which is necessary for tumor growth and metastasis. Effects on the Wnt/β-catenin Pathway: The Wnt/β-catenin signaling pathway, often dysregulated in several cancers (for example, colorectal cancer), may be modulated by vitamin D. Calcitriol has been shown in some models to inhibit β-catenin signaling, which is associated with decreased cell proliferation and tumor progression. Vitamin D may interact with other signaling pathways, including the PI3K/AKT/mTOR pathway, which is involved in cell survival and proliferation.
Time-Scale Flag (TSF): P / R / G
Clinical trial data suggest vitamin D supplementation effects may be attenuated in individuals with obesity, potentially due to pharmacokinetic and inflammatory differences.
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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 |
| 2369- | VitD3, | Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation |
| - | in-vitro, | CRC, | DLD1 | - | in-vitro, | CRC, | RKO |
| 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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:167 Target#:772 State#:% Dir#:1
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