Database Query Results : Curcumin, , GLO-I

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
- 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


GLO-I, glyoxalase I: Click to Expand ⟱
Source:
Type:
GLO-I, or glyoxalase I, is an enzyme that plays a crucial role in the detoxification of reactive carbonyl species, particularly methylglyoxal, which is a byproduct of various metabolic processes.
-Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs).
-Elevated levels of GLO-I in cancer cells can help them cope with these toxic byproducts, promoting cell survival and proliferation.
-High levels of GLO-I may be associated with tumor progression and poor prognosis in certain types of cancer.
-Inhibiting GLO-I could sensitize cancer cells to chemotherapy and other treatments by increasing their vulnerability to oxidative stress.
-Many studies have reported that GLO-I is overexpressed in several types of cancers, including breast, lung, prostate, colorectal, and pancreatic cancers. This overexpression is often associated with aggressive tumor behavior and poor prognosis.
Inhibitors: – Several flavonoids such as quercetin, luteolin, and fisetin have been shown to inhibit glyoxalase I activity in enzyme assays. - Curcumin. - Resveratrol - EGCG

Scientific Papers found: Click to Expand⟱
2823- CUR,    Binding of curcumin with glyoxalase I: Molecular docking, molecular dynamics simulations, and kinetics analysis
- Study, Nor, NA
GLO-I↓, recent studies demonstrate that the nature product curcumin is an efficient inhibitor of GLOI, but its binding mechanism towards GLOI is still unclear.

2822- CUR,    Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies
- Analysis, Nor, NA
GLO-I↓, In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM,

2654- CUR,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, ROS induction has been implicated as one of the mechanisms of the anticancer activity of curcumin and its derivatives in various cancers
Catalase↓, Curcumin induces ROS by inhibiting the activity of various ROS-related metabolic enzymes, such as CAT, SOD1, glyoxalase 1, and NAD(P)H dehydrogenase [quinone] 1 [146,149]
SOD1↓,
GLO-I↓,
NADPH↓,
TumCCA↑, ROS accumulation further mediates G1 or G2/M cell cycle arrest [146,147,150,154], senescence [146], and apoptosis.
Apoptosis↑,
Akt↓, downregulation of AKT phosphorylation [145
ER Stress↑, endoplasmic reticulum stress (namely through the PERK–ATF4–CHOP axis)
JNK↑, activation of the JNK pathway [151],
STAT3↓, and inhibition of STAT3 [155].
BioAv↑, Additionally, the combination of curcumin and piperine, a pro-oxidative phytochemical that drastically increases the bioavailability of curcumin in humans

409- CUR,    Curcumin Inhibits Glyoxalase 1—A Possible Link to Its Anti-Inflammatory and Anti-Tumor Activity
- in-vitro, Pca, PC3 - in-vitro, BC, MDA-MB-231
GLO-I↓,
GSH↓, 50uM
ATP↓, mostly >50uM


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Apoptosis↑,1,   ATP↓,1,   BioAv↑,1,   Catalase↓,1,   ER Stress↑,1,   GLO-I↓,4,   GSH↓,1,   JNK↑,1,   NADPH↓,1,   ROS↑,1,   SOD1↓,1,   STAT3↓,1,   TumCCA↑,1,  
Total Targets: 14

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: GLO-I, glyoxalase I
4 Curcumin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:65  Target#:125  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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