| Features: |
| 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 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 |
| Source: HalifaxProj(inhibit) CGL-CS TCGA |
| Type: |
| 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 responses. Anti-inflammatory cytokine. In normal tissues, TGF-β plays an essential role in cell cycle regulation, immune function, and tissue remodeling. - In early carcinogenesis, TGF-β typically acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. In advanced cancers, cells frequently become resistant to the growth-inhibitory effects of TGF-β. - TGF-β then switches roles and promotes tumor progression by stimulating epithelial-to-mesenchymal transition (EMT), cell invasion, metastasis, and immune evasion. Non-canonical (Smad-independent) pathways, such as MAPK, PI3K/Akt, and Rho signaling, also contribute to TGF-β-mediated responses. Elevated levels of TGF-β have been detected in many advanced-stage cancers, including breast, lung, colorectal, pancreatic, and prostate cancers. - The switch from a tumor-suppressive to a tumor-promoting role is often associated with increased TGF-β production and activation in the tumor microenvironment. High TGF-β expression or signaling activity is frequently correlated with aggressive disease features, resistance to therapy, increased metastasis, and poorer overall survival in many cancer types. |
| 447- | CUR, | OXA, | Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway |
| - | vitro+vivo, | CRC, | HCT116 |
| 153- | CUR, | Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo |
| - | in-vivo, | Pca, | C4-2B |
| 13- | CUR, | Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action |
| - | Review, | BC, | NA |
| 124- | CUR, | Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells |
| - | in-vitro, | Pca, | LNCaP | - | in-vitro, | Pca, | C4-2B |
| 3582- | CUR, | PI, | Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte Cells |
| 2688- | CUR, | Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 103- | RES, | CUR, | QC, | The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice |
| - | vitro+vivo, | BC, | 4T1 |
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