Curcumin / MMP 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↓">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


MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱
Source:
Type:
Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.


Scientific Papers found: Click to Expand⟱
4415- AgNPs,  SDT,  CUR,    Examining the Impact of Sonodynamic Therapy With Ultrasound Wave in the Presence of Curcumin-Coated Silver Nanoparticles on the Apoptosis of MCF7 Breast Cancer Cells
- in-vitro, BC, MCF-7
tumCV↓, BAX↑, Casp3↑, Bcl-2↓, eff↑, ROS↑, sonoS↑, eff↑, MMP↓, Cyt‑c↑,
2980- CUR,    Inhibition of NF B and Pancreatic Cancer Cell and Tumor Growth by Curcumin Is Dependent on Specificity Protein Down-regulation
- in-vivo, PC, NA
TumCG↓, p50↓, p65↓, NF-kB↓, Sp1/3/4↓, MMP↓, ROS↑,
462- CUR,    Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress
- in-vitro, Pca, PC3
Bcl-2↓, MMP↓, cl‑Casp3↑, BAX↑, BIM↑, p‑PARP↑, PUMA↑, p‑P53↑, ROS↑, p‑ERK↑, p‑eIF2α↑, CHOP↑, ATF4↑,
1409- CUR,    Curcumin analog WZ26 induces ROS and cell death via inhibition of STAT3 in cholangiocarcinoma
- in-vivo, CCA, Walker256
TumCG↓, ROS↑, MMP↓, STAT3↓, TumCCA↑, eff↓,
1981- CUR,    Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity
- in-vitro, Lung, NA
eff↑, ROS↑, mt-GSH↓, Bax:Bcl2↑, Cyt‑c↑, MMP↓, Casp3↑, Trx2↓, TrxR↓, mt-DNAdam↑,
481- CUR,  CHr,  Api,    Flavonoid-induced glutathione depletion: Potential implications for cancer treatment
- in-vitro, Liver, A549 - in-vitro, Pca, PC3 - in-vitro, AML, HL-60
GSH↓, mtDam↑, MMP↓, Cyt‑c↑,
407- CUR,    Curcumin inhibited growth of human melanoma A375 cells via inciting oxidative stress
- in-vitro, Melanoma, A375
Apoptosis↑, ROS↑, GSH↓, MMP↓,
831- GAR,  CUR,    Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells
- in-vitro, AML, HL-60
Apoptosis↑, Casp3↑, MMP↓, Cyt‑c↑, proCasp9↑, Bcl-2↓, BAX↑, PARP↓, DNAdam↑, DFF45↓,
138- QC,  CUR,    Sensitization of androgen refractory prostate cancer cells to anti-androgens through re-expression of epigenetically repressed androgen receptor - Synergistic action of quercetin and curcumin
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
DNMTs↓, AR↑, MMP↓,
4827- QC,  CUR,    Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin
- Review, Var, NA
*AntiCan↑, *Inflam↓, *Bacteria↓, *AntiDiabetic↑, *ROS↓, *SOD↑, *Catalase↑, *GSH↑, *NRF2↑, *Trx↑, *IronCh↑, *MDA↑, cycD1/CCND1↓, PI3K↓, Casp3↑, BAX↑, ChemoSen↑, ROS↑, eff↑, MMP↓, Cyt‑c↑, Akt↓, ERK↓,
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
ROS↑, MMP↓, Bcl-2↓, BAX↑, Casp9↑, T-Cell↑, TGF-β↓,
871- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- in-vitro, BC, 4T1 - in-vivo, BC, 4T1
T-Cell↑, Neut↓, Macrophages↓, ROS↑, MMP↓, other↓, AntiTum↑, TumVol↓,

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

GSH↓, 2,   mt-GSH↓, 1,   ROS↑, 9,   Trx2↓, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics

MMP↓, 12,   mtDam↑, 1,  

Cell Death

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 5,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   BIM↑, 1,   Casp3↑, 4,   cl‑Casp3↑, 1,   Casp9↑, 1,   proCasp9↑, 1,   Cyt‑c↑, 5,   PUMA↑, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Transcription & Epigenetics

other↓, 1,   sonoS↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

CHOP↑, 1,   p‑eIF2α↑, 1,  

DNA Damage & Repair

DFF45↓, 1,   DNAdam↑, 1,   mt-DNAdam↑, 1,   DNMTs↓, 1,   p‑P53↑, 1,   PARP↓, 1,   p‑PARP↑, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

ERK↓, 1,   p‑ERK↑, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 2,  

Migration

TGF-β↓, 1,  

Angiogenesis & Vasculature

ATF4↑, 1,  

Immune & Inflammatory Signaling

Macrophages↓, 1,   Neut↓, 1,   NF-kB↓, 1,   p50↓, 1,   p65↓, 1,   T-Cell↑, 2,  

Hormonal & Nuclear Receptors

AR↑, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   eff↓, 1,   eff↑, 4,  

Clinical Biomarkers

AR↑, 1,  

Functional Outcomes

AntiTum↑, 1,   TumVol↓, 1,  
Total Targets: 54

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

Catalase↑, 1,   GSH↑, 1,   MDA↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,   Trx↑, 1,  

Metal & Cofactor Biology

IronCh↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Functional Outcomes

AntiCan↑, 1,   AntiDiabetic↑, 1,  

Infection & Microbiome

Bacteria↓, 1,  
Total Targets: 12

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential
12 Curcumin
4 Quercetin
2 Resveratrol
1 Silver-NanoParticles
1 SonoDynamic Therapy UltraSound
1 Chrysin
1 Apigenin (mainly Parsley)
1 Garcinol
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#:197  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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