Curcumin / MMP9 Cancer Research Results

CUR, Curcumin: Click to Expand ⟱
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
-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

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of survival and inflammatory transcription NF-κB is a primary, repeatedly validated curcumin target explaining pleiotropic downstream effects
2 STAT3 signaling ↓ STAT3 phosphorylation / activity ↔ or mild suppression Driver Loss of pro-survival and proliferative signaling STAT3 inhibition contributes to growth arrest, apoptosis sensitization, and reduced cytokine signaling in tumors
3 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Curcumin can act as a pro-oxidant in cancer cells with high basal stress while acting antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and caspase activation occur downstream of NF-κB/STAT3 and ROS effects
5 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ or adaptive suppression Secondary Reduced growth and anabolic signaling AKT/mTOR inhibition contributes to growth suppression and autophagy induction in cancer cells
6 Autophagy ↑ autophagy (protective or pro-death) ↑ adaptive autophagy Secondary Stress adaptation vs cell death Autophagy may be cytoprotective or cooperate with apoptosis depending on context and dose
7 HIF-1α / VEGF hypoxia–angiogenesis axis ↓ HIF-1α; ↓ VEGF ↔ minimal effect Secondary Anti-angiogenic pressure Suppression of hypoxia-driven transcription limits angiogenesis and tumor adaptation
8 Cell cycle regulation ↑ G2/M or G1 arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling and epigenetic effects rather than direct CDK inhibition
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT markers and protease activity limit invasive behavior
10 Epigenetic regulation (p300/CBP HAT activity) ↓ histone acetylation ↔ modest Secondary Transcriptional reprogramming Curcumin modulates chromatin via HAT inhibition rather than classic HDAC inhibition


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
4675- CUR,    Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines
- in-vitro, NSCLC, A549
ChemoSen↑, CSCs↓, EpCAM↓, TumCCA↓, VEGF↓, MMP9↓, toxicity↓,
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
TumCMig↓, TumCI↓, TumCG↓, TumMeta↓, Sp1/3/4↓, HDAC4↓, FAK↓, CD24↓, E-cadherin↑, EMT↓, TumCP↓, NF-kB↓, AP-1↝, STAT3↓, P53?, β-catenin/ZEB1↓, NOTCH1↝, Hif1a↝, PPARα↝, Rho↓, MMP2↓, MMP9↓,
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
*ROS↓, *SOD↑, p16↑, JAK2↓, STAT3↓, CXCL12↓, IL6↓, MMP2↓, MMP9↓, TGF-β↓, α-SMA↓, LAMs↓, DNAdam↑, *memory↑, *cognitive↑, *Inflam↓, *antiOx↑, *NO↑, *MDA↓, *ROS↓, DNMT1↓, ROS↑, Casp3↑, Apoptosis↑, miR-21↓, LC3II↓, ChemoSen↑, NF-kB↓, CSCs↓, Nanog↓, OCT4↓, SOX2↓, eff↑, Sp1/3/4↓, miR-27a-3p↓, ZBTB10↑, SOX9?, ChemoSen↑, VEGF↓, XIAP↓, Bcl-2↓, cycD1/CCND1↓, BioAv↑, Hif1a↓, EMT↓, BioAv↓, PTEN↑, VEGF↓, Akt↑, EZH2↓, NOTCH1↓, TP53↑, NQO1↑, HO-1↑,
2466- CUR,    Regulatory Effects of Curcumin on Platelets: An Update and Future Directions
- Review, Nor, NA
*AntiAg↑, *antiOx↑, *Inflam↓, *12LOX↑, COX1↓, COX2↓, MMP9↓, NF-kB↓,
464- CUR,    Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR-301a-3p/STAT3 axis
- in-vitro, Thyroid, BCPAP - in-vitro, Thyroid, TPC-1
TumCI↓, TumCI↓, MMP2↓, MMP9↓, EMT↓, STAT3↓, miR-301a-3p↓, STAT↓, N-cadherin↓, Vim↓, Fibronectin↓, p‑JAK↓, p‑JAK2↓, p‑JAK3↓, p‑STAT1↓, p‑STAT2↓, E-cadherin↑,
433- CUR,    Curcumin Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer Cells Through Radiation-Induced Suppression of Epithelial-Mesenchymal Transition and Soluble E-Cadherin Expression
- in-vitro, Lung, A549
E-cadherin↓, Vim↓, Slug↓, N-cadherin↓, Snail↓, MMP9↓, EMT↓,
1418- CUR,    Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis
- Review, Arthritis, NA
*COX2↓, *Inflam↓, *5LO↓, *NO↓, *NF-kB↓, *TNF-α↓, *IL1↓, *IL2↑, *IL6↓, *IL8↓, *IL12↓, *MCP1↓, *PGE2↓, *MMP2↓, *MMP3↓, *MMP9↓, *NLRP3↓, *ROS↓,
473- CUR,    Curcumin inhibits epithelial-mesenchymal transition in oral cancer cells via c-Met blockade
- in-vitro, Oral, HSC4 - in-vitro, Oral, Ca9-22
Vim↓, p‑cMET↓, p‑ERK↓, pro‑MMP9↓, E-cadherin↑,
155- CUR,    Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells
- in-vitro, Pca, PC3
p‑ERK↓, VEGF↓, angioG↓, MMP2↓, MMP9↓, angioS↑,
158- CUR,    Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis
- vitro+vivo, Pca, LNCaP - in-vitro, Pca, PC3
MMP9↓, Matr↓, Inflam↓, antiOx↓, NF-kB↓, COX2↓, iNOS↓, TumCMig↓, TumCI↓,
181- CUR,    The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo
- vitro+vivo, Pca, DU145
MMP2↓, MMP9↓, TumCP↓, TumCI↓,
170- CUR,    Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis
- vitro+vivo, Pca, PC3
TRAILR↑, BAX↑, P21↑, p27↑, NF-kB↓, cycD1/CCND1↓, VEGF↓, uPA↓, MMP2↓, MMP9↓, Bcl-2↓, Bcl-xL↓,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   HO-1↑, 1,   NQO1↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

PPARα↝, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 2,   Bcl-xL↓, 1,   Casp3↑, 1,   iNOS↓, 1,   p27↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

SOX9?, 1,   Sp1/3/4↓, 2,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   Matr↓, 1,   miR-21↓, 1,   miR-27a-3p↓, 1,  

Autophagy & Lysosomes ⓘ

LC3II↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   p16↑, 1,   P53?, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   P21↑, 1,   TumCCA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   p‑cMET↓, 1,   CSCs↓, 2,   EMT↓, 4,   EpCAM↓, 1,   p‑ERK↓, 2,   HDAC4↓, 1,   Nanog↓, 1,   NOTCH1↓, 1,   NOTCH1↝, 1,   OCT4↓, 1,   PTEN↑, 1,   SOX2↓, 1,   STAT↓, 1,   p‑STAT1↓, 1,   p‑STAT2↓, 1,   STAT3↓, 3,   TumCG↓, 1,  

Migration ⓘ

AP-1↝, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 3,   FAK↓, 1,   Fibronectin↓, 1,   LAMs↓, 1,   miR-301a-3p↓, 1,   MMP2↓, 6,   MMP9↓, 10,   pro‑MMP9↓, 1,   N-cadherin↓, 2,   Rho↓, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 5,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   uPA↓, 1,   Vim↓, 3,   α-SMA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   angioS↑, 1,   Hif1a↓, 1,   Hif1a↝, 1,   VEGF↓, 5,   ZBTB10↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 2,   IL6↓, 1,   Inflam↓, 1,   p‑JAK↓, 1,   JAK2↓, 1,   p‑JAK2↓, 1,   p‑JAK3↓, 1,   NF-kB↓, 5,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 3,   eff↑, 1,  

Clinical Biomarkers ⓘ

EZH2↓, 1,   IL6↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 95

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   MDA↓, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↑, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 1,   MMP2↓, 1,   MMP3↓, 1,   MMP9↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   NO↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 3,   MCP1↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,  
Total Targets: 27

Scientific Paper Hit Count for: MMP9, MMP9
12 Curcumin
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#:65  Target#:203  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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