condition found tbRes List
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

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


MMPs, Matrix metalloproteinases: Click to Expand ⟱
Source:
Type:
Family of zinc-dependent proteolytic enzymes that play a key role in degrading the extracellular matrix (ECM).; are metalloproteinases that are calcium-dependent zinc-containing endopeptidases;[1] other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.[2]
MMP secretion: matrix metalloproteinase (MMP) is a kind of enzymes secreted.
by tumor cell to degrade ECM, facilitating the migration of tumor cells.

MMPs are generally considered protumorigenic due to their role in promoting tumor invasion, metastasis, and angiogenesis. They facilitate the breakdown of the extracellular matrix, allowing cancer cells to invade surrounding tissues and spread to distant sites.
Scientific Papers found: Click to Expand⟱
1792- CUR,  LEC,    Chondroprotective effect of curcumin and lecithin complex in human chondrocytes stimulated by IL-1β via an anti-inflammatory mechanism
- in-vitro, Arthritis, RAW264.7 - NA, NA, HCC-38
*Inflam↓, curcumin is well known to regulate anti-inflammatory effects, primarily through the deactivation of NF-κB
*NF-kB↓,
*iNOS↓, 10 and 20 μM, complex also suppressed iNOS and COX-2 mRNA expression and inhibited NO and PGE2 production
*COX2↓,
*NO↓,
*PGE2↓,
*MMPs↑, 10 and 20 μM of the complex (Fig. 2A, B, and C). IL-1β noticeably upregulated the production of MMP-1, 2, 3, 9, and 13 and TIMP-1 compared to the control group
*TIMP1↑,
*BioEnh↑, In this study, the complex of curcumin and lecithin enhanced bioavailability of curcumin resulting in chondroprotective effect at relatively lower concentrations.

13- CUR,    Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action
- Review, BC, NA
P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

3583- CUR,    Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers
- Review, Arthritis, NA
*TNF-α↓, Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans
*IL1β↓, curcumin has been found to down-regulate the expression of TNF-α and IL-1β in ankle joints and decrease NF-κB activity, PGE2 production, COX-2 expression and MMP secretion in synoviocytes.
*NF-kB↓,
*PGE2↓,
*COX2↓,
*MMPs↓,
*eff↑, curcumin has been shown to have a synergistic effect with methotrexate in decreasing adjuvant-induced arthritis in mice


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
ATPase↓,1,   COX2↓,1,   DR5↑,1,   EGFR↓,1,   ER(estro)↓,1,   Fas↑,1,   FGF↓,1,   HER2/EBBR2↓,1,   IL1↓,1,   IL12↓,1,   IL18↓,1,   IL2↓,1,   IL5↓,1,   IL6↓,1,   IL8↓,1,   IR↓,1,   JAK↓,1,   JNK↑,1,   MAPK↓,1,   MMPs↓,1,   NF-kB↓,1,   NOTCH1↓,1,   NRF2↑,1,   P53↑,1,   PAK↓,1,   PDGF↓,1,   PPARγ↑,1,   STAT1↓,1,   STAT3↓,1,   STAT4↓,1,   STAT5↓,1,   TGF-β↓,1,  
Total Targets: 32

Results for Effect on Normal Cells:
BioEnh↑,1,   COX2↓,2,   eff↑,1,   IL1β↓,1,   Inflam↓,1,   iNOS↓,1,   MMPs↓,1,   MMPs↑,1,   NF-kB↓,2,   NO↓,1,   PGE2↓,2,   TIMP1↑,1,   TNF-α↓,1,  
Total Targets: 13

Scientific Paper Hit Count for: MMPs, Matrix metalloproteinases
3 Curcumin
1 Lecithin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:65  Target#:204  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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