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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 - 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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| TrxR is an enzyme that reduces Trx, allowing it to perform its reducing functions. It has been shown to have a role in cancer cell metabolism and survival. TrxR is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. - Part of the thioredoxin system, which regulates reactive oxygen species (ROS). - TrxR is a major antioxidant systems that maintains the intracellular redox homeostasis. - Inhibition causes an increase in ROS. - TrxR is often upregulated in cancer cells to help manage increased oxidative stress, it is seen as a potential therapeutic target. Inhibiting TrxR may result in increased ROS in cancer cells, pushing them toward apoptosis. - TrxR is a selenoprotein—meaning it incorporates the trace element selenium in the form of the amino acid selenocysteine. TrxR inhibitors: -Piperlongumine -Withania somnifera (Ashwagandha) -Parthenolide -EGCG -Curcumin -Myricetin -Gambogic Acid |
| 1980- | CUR, | Rad, | Thioredoxin reductase-1 (TxnRd1) mediates curcumin-induced radiosensitization of squamous carcinoma cells |
| - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Laryn, | FaDu |
| 1977- | CUR, | Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Lung, | A549 |
| 1979- | CUR, | Rad, | Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase |
| - | in-vitro, | Lung, | A549 |
| 1981- | CUR, | Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity |
| - | in-vitro, | Lung, | NA |
| 1982- | CUR, | Inhibition of thioredoxin reductase by curcumin analogs |
| - | in-vitro, | NA, | NA |
| 1998- | Myr, | CUR, | Thioredoxin-dependent system. Application of inhibitors |
| - | Review, | Var, | NA |
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