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| Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties. - Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells. - GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells. - Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production - Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant - Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH - Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown -may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog). Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans. • Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability. -Note half-life 6 hrs. BioAv is poor, use piperine or other enhancers Pathways: - induce ROS production at high concentration. Lowers ROS at lower concentrations curcumin can act as a pro-oxidant when blue light is applied - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ - Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓ but conversely is known as a NRF2↑ activator in cancer - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓, - inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells
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| Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. – As a rate-limiting enzyme in glycolysis, PFK1 is subject to complex regulation through allosteric effectors including ATP, AMP, and fructose-2,6-bisphosphate. • Metabolic Control: –PFK1 activity is central to controlling the pace of glycolysis, thereby influencing energy production and intermediary metabolite supply. – In highly proliferative cells or cells under growth conditions, increased glycolytic flux (and, by extension, PFK1 activity) supports the biosynthetic demands of cell division. – Many tumors (including breast, colorectal, and lung cancers) have been reported to have increased PFK1 expression/activity relative to normal tissues. – High glycolytic flux, driven partly by enhanced PFK1, supports rapid cell proliferation and survival in the nutrient/stress-challenged tumor microenvironment. Inhibitors:(typically glycolysis is targeted more broadly) -Citrate -Hydrogen ions (pH) – Acidic conditions can have inhibitory effects. -3PO: inhibits PFKFB3, thereby indirectly reducing PFK1 activity. -Resveratrol can downregulate glycolytic flux in cancer cells, which may indirectly affect PFK1 activity. - FMDs offer an indirect strategy to modulate cancer metabolism by broadly reducing glycolysis. Their impact on PFK1 is likely part of a complex network of metabolic adaptations rather than a direct inhibitory effect. |
| 2308- | CUR, | Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells |
| - | in-vitro, | Liver, | HepG2 |
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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