| 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: TCGA |
| Type: Proapototic |
| TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures. p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress. TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers. Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53. In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein. Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver. |
| 462- | CUR, | Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress |
| - | in-vitro, | Pca, | PC3 |
| 477- | CUR, | Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells |
| - | in-vitro, | Cerv, | SiHa |
| 454- | CUR, | Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway |
| - | in-vitro, | GC, | MGC803 |
| 457- | CUR, | Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling |
| - | in-vitro, | GC, | SGC-7901 | - | in-vitro, | GC, | BGC-823 |
| 1609- | CUR, | EA, | Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells |
| - | in-vitro, | Cerv, | NA |
| 2308- | CUR, | Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells |
| - | in-vitro, | Liver, | HepG2 |
| 136- | CUR, | docx, | Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer |
| - | in-vitro, | Pca, | DU145 | - | in-vitro, | Pca, | PC3 |
| 137- | CUR, | Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling |
| - | in-vitro, | Pca, | DU145 |
| 13- | CUR, | Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action |
| - | Review, | BC, | NA |
| 15- | CUR, | UA, | Effects of curcumin and ursolic acid in prostate cancer: A systematic review |
| 424- | CUR, | Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-231 |
| 2974- | CUR, | Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | CRC, | HT29 | - | in-vitro, | CRC, | HCT15 | - | in-vitro, | CRC, | COLO205 | - | in-vitro, | CRC, | SW-620 | - | in-vivo, | NA, | NA |
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