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


α-SMA, α-smooth muscle actin: Click to Expand ⟱
Source:
Type: protein
α-smooth muscle actin (α-SMA) is a protein that is often associated with cancer progression. It is a key component of the actin cytoskeleton and plays a crucial role in cell migration, invasion, and contraction.
α-SMA is often expressed by cancer-associated fibroblasts (CAFs), which are a type of stromal cell that surrounds the tumor. CAFs expressing α-SMA can promote tumor growth and metastasis.
High levels of α-SMA expression have been correlated with poor prognosis in various types of cancer, including breast, lung, and colorectal cancer.
Scientific Papers found: Click to Expand⟱
3446- ALA,  CUR,    The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression
- in-vivo, Nor, NA
*hepatoP↑, Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.
*α-SMA↓, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication
*COL3A1↓,
*ROS↓, scavenging activity to ROS and a capacity to regenerate endogenous antioxidants such as GSH, and vitamins C and E.
*GSH↑,
*ALAT↓, ALT, AST, and ALP activity levels compared to those of the control group. The use of NACS, Curc, and/or Lip acid significantly reduced the toxic effects of NHPA on those enzymes,
*AST↓,
*ALP↓,
*MDA↓, The combination therapy showed an apparent reduction in MDA level more than other treatments

465- CUR,    Curcumin inhibits the growth of liver cancer by impairing myeloid-derived suppressor cells in murine tumor tissues
- vitro+vivo, Liver, HepG2 - vitro+vivo, Liver, HUH7 - vitro+vivo, Liver, MHCC-97H
TumCG↓,
MDSCs↓,
TLR4↓,
NF-kB↓,
IL6↓,
IL1↓, IL-1β
PGE2↓,
COX2↓,
GM-CSF↓,
angioG↓,
VEGF↓,
CD31↓,
GM-CSF↓,
α-SMA↓,
p‑IKKα↓, p-IKKα, p-IKKβ
MyD88↓,

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↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↓,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,


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

Results for Effect on Cancer/Diseased Cells:
Akt↑,1,   angioG↓,1,   Apoptosis↑,1,   Bcl-2↓,1,   BioAv↓,1,   BioAv↑,1,   Casp3↑,1,   CD31↓,1,   ChemoSen↑,2,   COX2↓,1,   CSCs↓,1,   CXCL12↓,1,   cycD1↓,1,   DNAdam↑,1,   DNMT1↓,1,   eff↑,1,   EMT↓,1,   EZH2↓,1,   GM-CSF↓,2,   Hif1a↓,1,   HO-1↑,1,   p‑IKKα↓,1,   IL1↓,1,   IL6↓,2,   JAK2↓,1,   LAMs↓,1,   LC3II↓,1,   MDSCs↓,1,   miR-21↓,1,   miR-27a-3p↓,1,   MMP2↓,1,   MMP9↓,1,   MyD88↓,1,   Nanog↓,1,   NF-kB↓,2,   NOTCH1↓,1,   NQO1↑,1,   OCT4↓,1,   p16↑,1,   PGE2↓,1,   PTEN↑,1,   ROS↑,1,   SOX2↓,1,   SOX9?,1,   Sp1/3/4↓,1,   STAT3↓,1,   TGF-β↓,1,   TLR4↓,1,   TP53↑,1,   TumCG↓,1,   VEGF↓,3,   XIAP↓,1,   ZBTB10↑,1,   α-SMA↓,2,  
Total Targets: 54

Results for Effect on Normal Cells:
ALAT↓,1,   ALP↓,1,   antiOx↓,1,   AST↓,1,   cognitive↑,1,   COL3A1↓,1,   GSH↑,1,   hepatoP↑,1,   Inflam↓,1,   MDA↓,2,   memory↑,1,   NO↑,1,   ROS↓,3,   SOD↑,1,   α-SMA↓,1,  
Total Targets: 15

Scientific Paper Hit Count for: α-SMA, α-smooth muscle actin
3 Curcumin
1 Alpha-Lipoic-Acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:65  Target#:719  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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