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


cycD1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
1426- Bos,  CUR,  Chemo,    Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer
- in-vivo, CRC, NA - in-vitro, CRC, HCT116 - in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vitro, RCC, SW-620 - in-vitro, RCC, HT-29 - in-vitro, CRC, Caco-2
miR-34a↑, curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells
miR-27a-3p↓,
TumCG↓,
BAX↑,
Bcl-2↓,
PARP1↓,
TumCCA↑,
Apoptosis↑,
cMyc↓,
CDK4↓,
CDK6↓,
cycD1↓,
ChemoSen↑, combined treatment further increased the inhibitory effects
miR-34a↑, miR-34a expression was upregulated by curcumin and further elevated by concurrent treatment with curcumin and AKBA in HCT116 cell
miR-27a-3p↓,

470- CUR,    Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line
- in-vitro, Ovarian, SKOV3
Wnt/(β-catenin)↓,
EMT↓,
DNMT3A↓,
cycD1↓,
cMyc↓,
Fibronectin↓,
Vim↓,
E-cadherin↑,
SFRP5↑,

9- CUR,    Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/GLI1 Signaling Pathway in Vitro and Vivo
- vitro+vivo, MG, U87MG - vitro+vivo, MG, T98G
HH↓,
Shh↓,
Gli1↓,
cycD1↓,
Bcl-2↓,
Foxm1↓,
Bax:Bcl2↑,

456- CUR,    Curcumin Promoted miR-34a Expression and Suppressed Proliferation of Gastric Cancer Cells
- vitro+vivo, GC, SGC-7901
miR-34a↑,
TumCP↓,
TumCMig↓,
TumCI↓,
TumCCA↑, inhibited cell cycle progression in G0/G1-S phase
Bcl-2↓,
CDK4/6↓, CDK4
cycD1↓,

137- CUR,    Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling
- in-vitro, Pca, DU145
NOTCH1↓,
cycD1↓,
CDK2↓,
P21↑,
p27↑,
P53↑,
Bcl-2↓,
Casp3↑,
Casp9↑,

12- CUR,    Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells
- in-vitro, MB, DAOY
HH↓,
Shh↓,
Gli1↓,
PTCH1↓,
cMyc↓,
n-MYC↓,
cycD1↓,
Bcl-2↓,
NF-kB↓,
Akt↓,
β-catenin/ZEB1↓,
survivin↓,

15- CUR,  UA,    Effects of curcumin and ursolic acid in prostate cancer: A systematic review
NF-kB↝,
Akt↝,
AR↝,
Apoptosis↝,
Bcl-2↝,
Casp3↝,
BAX↝,
P21↝,
ROS↝,
Apoptosis↝,
Bcl-xL↝,
JNK↝,
MMP2↝,
P53↝,
PSA↝,
VEGF↝,
COX2↝,
cycD1↝,
EGFR↝,
IL6↝,
β-catenin/ZEB1↝,
mTOR↝,
NRF2↝,
p‑Akt↝,
AP-1↝,
Cyt‑c↝,
PI3K↝,
PTEN↝,
Cyc↝,
TNF-α↝,

126- CUR,    Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vitro, Pca, DU145
miR-34a↑,
β-catenin/ZEB1↓,
cMyc↓,
P21↑,
cycD1↓,
PCNA↓,

437- CUR,    Anti-cancer activity of amorphous curcumin preparation in patient-derived colorectal cancer organoids
- vitro+vivo, CRC, TCO1 - vitro+vivo, CRC, TCO2
cycD1↓,
cMyc↓,
p‑ERK↓,
CD44↓,
CD133↓,
LGR5↓,
TumCCA↑, proportion of cells in the G0/G1 phase in CRC organoids significantly increased at 24 h
TumVol↓,

165- CUR,    Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓,
β-catenin/ZEB1↓,
p‑Akt↓,
GSK‐3β↓,
p‑β-catenin/ZEB1↑, phosphorylated
cycD1↓,
cMyc↓,

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↓,
VEGF↓,
uPA↓,
MMP2↓,
MMP9↓,
Bcl-2↓,
Bcl-xL↓,

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: 12

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Akt↑,1,   Akt↝,1,   p‑Akt↓,1,   p‑Akt↝,1,   AP-1↝,1,   Apoptosis↑,2,   Apoptosis↝,2,   AR↓,1,   AR↝,1,   BAX↑,2,   BAX↝,1,   Bax:Bcl2↑,1,   Bcl-2↓,7,   Bcl-2↝,1,   Bcl-xL↓,1,   Bcl-xL↝,1,   BioAv↓,1,   BioAv↑,1,   Casp3↑,2,   Casp3↝,1,   Casp9↑,1,   CD133↓,1,   CD44↓,1,   CDK2↓,1,   CDK4↓,1,   CDK4/6↓,1,   CDK6↓,1,   ChemoSen↑,3,   cMyc↓,6,   COX2↝,1,   CSCs↓,1,   CXCL12↓,1,   Cyc↝,1,   cycD1↓,11,   cycD1↝,1,   Cyt‑c↝,1,   DNAdam↑,1,   DNMT1↓,1,   DNMT3A↓,1,   E-cadherin↑,1,   eff↑,1,   EGFR↝,1,   EMT↓,2,   p‑ERK↓,1,   EZH2↓,1,   Fibronectin↓,1,   Foxm1↓,1,   Gli1↓,2,   GSK‐3β↓,1,   HH↓,2,   Hif1a↓,1,   HO-1↑,1,   IL6↓,1,   IL6↝,1,   JAK2↓,1,   JNK↝,1,   LAMs↓,1,   LC3II↓,1,   LGR5↓,1,   miR-21↓,1,   miR-27a-3p↓,3,   miR-34a↑,4,   MMP2↓,2,   MMP2↝,1,   MMP9↓,2,   mTOR↝,1,   n-MYC↓,1,   Nanog↓,1,   NF-kB↓,3,   NF-kB↝,1,   NOTCH1↓,2,   NQO1↑,1,   NRF2↝,1,   OCT4↓,1,   p16↑,1,   P21↑,3,   P21↝,1,   p27↑,2,   P53↑,1,   P53↝,1,   PARP1↓,1,   PCNA↓,1,   PI3K↝,1,   PSA↝,1,   PTCH1↓,1,   PTEN↑,1,   PTEN↝,1,   ROS↑,1,   ROS↝,1,   SFRP5↑,1,   Shh↓,2,   SOX2↓,1,   SOX9?,1,   Sp1/3/4↓,1,   STAT3↓,1,   survivin↓,1,   TGF-β↓,1,   TNF-α↝,1,   TP53↑,1,   TRAILR↑,1,   TumCCA↑,3,   TumCG↓,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   TumVol↓,1,   uPA↓,1,   VEGF↓,3,   VEGF↝,1,   Vim↓,1,   Wnt/(β-catenin)↓,1,   XIAP↓,1,   ZBTB10↑,1,   α-SMA↓,1,   β-catenin/ZEB1↓,3,   β-catenin/ZEB1↝,1,   p‑β-catenin/ZEB1↑,1,  
Total Targets: 118

Results for Effect on Normal Cells:
antiOx↓,1,   cognitive↑,1,   Inflam↓,1,   MDA↓,1,   memory↑,1,   NO↑,1,   ROS↓,2,   SOD↑,1,  
Total Targets: 8

Scientific Paper Hit Count for: cycD1, cyclin D1 pathway
12 Curcumin
1 Boswellia (frankincense)
1 Chemotherapy
1 Ursolic acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:65  Target#:73  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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