PPARα Cancer Research Results

PPARα, Peroxisome Proliferator-Activated Receptor Alpha: Click to Expand ⟱
Source:
Type:
• PPARα
– Regulates fatty acid oxidation, lipid metabolism, and energy homeostasis.
– Expressed primarily in liver, heart, kidney, and muscle, PPARα activation induces genes involved in β-oxidation and lipid transport.
– It is also involved in modulating inflammatory responses, which may indirectly affect cellular proliferation and survival.

– Expression and activation in cancers can vary:
– In some liver cancers, PPARα expression or activity may be altered, reflecting its central role in hepatic metabolism.
– Overactivation has been associated with liver proliferation in rodent models; however, species differences exist regarding the carcinogenic potential of PPARα agonists.
– Outside the liver, PPARα’s role is less defined, but its regulation of inflammation and lipid metabolism may influence tumor metabolism and microenvironment.
Scientific Papers found: Click to Expand⟱
2767- Bos,    The potential role of boswellic acids in cancer prevention and treatment
- Review, Var, NA
*Inflam↓, profound application as a traditional remedy for various ailments, especially inflammatory diseases including asthma, arthritis, cerebral edema, chronic pain syndrome, chronic bowel diseases, cancer
AntiCan↑,
*MAPK↑, 11-keto-BAs can stimulate Mitogen-activated protein kinases (MAPK) and mobilize the intracellular Ca(2+) that are important for the activation of human polymorphonuclear leucocytes (PMNL)
*Ca+2↝,
p‑ERK↓, AKBA prohibited the phosphorylation of extracellular signal-regulated kinase-1 and -2 (Erk-1/2) and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB
TumCI↓,
cycD1/CCND1↓, In the case of colon cancer, BA treatment on HCT-116 cells led to a decrease in cyclin D, cyclin E, and Cyclin-dependent kinases such as CDK2 and CDK4, along with significant reduction in phosphorylated Rb (pRb)
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p‑RB1↓,
*NF-kB↓, convey inhibition of NF-kappaB and subsequent down-regulation of TNF-alpha expression in activated human monocytes
*TNF-α↓,
NF-kB↓, PC-3 prostate cancer cells in vitro and in vivo by inhibiting constitutively activated NF-kappaB signaling by intercepting the activity of IkappaB kinase (IKK
IKKα↓,
MCP1↓, LPS-challenged ApoE-/- mice via inhibition of NF-κB and down regulation of MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF
IL1α↓,
MIP2↓,
VEGF↓,
Tf↓,
COX2↓, pancreatic cancer cell lines, AKBA inhibited the constitutive expression of NF-kB and caused suppression of NF-kB regulated genes such as COX-2, MMP-9, CXCR4, and VEGF
MMP9↓,
CXCR4↓,
VEGF↓,
eff↑, AKBA and aspirin revealed that AKBA has higher potential via modulation of the Wnt/β-catenin pathway, and NF-kB/COX-2 pathway in adenomatous polyps
PPARα↓, AKBA is also responsible for down-regulation of PPAR-alpha and C/EBP-alpha in a dose and temporal dependent manner in mature adipocytes, ultimately leading to pparlipolysis
lipid-P?,
STAT3↓, activation of STAT-3 in human MM cells could be inhibited by AKBA
TOP1↓, (PKBA; a semisynthetic analogue of 11-keto-β-boswellic acid), had been reported to influence the activity of topoisomerase I & II,
TOP2↑,
5HT↓, (5-LO), responsible for catalyzing the synthesis of leukotrienes from arachidonic acid and human leucocyte elastase (HLE), and serine proteases involved in several inflammatory processes, is considered to be a potent molecular target of BA derivative
p‑PDGFR-BB↓, BA up-regulates SHP-1 with subsequent dephosphorylation of PDGFR-β and downregulation of PDGF-dependent signaling after PDGF stimulation, thereby exerting an anti-proliferative effect on HSCs hepatic stellate cells
PDGF↓,
AR↓, AKBA targets different receptors that include androgen receptor (AR), death receptor 5 (DR5), and vascular endothelial growth factor receptor 2 (VEGFR2), and leads to the inhibition of proliferation of prostate cancer cells
DR5↑, induced expression of DR4 and DR5.
angioG↓, via apoptosis induction and suppression of angiogenesis
DR4↑,
Casp3↑, AKBA resulted in activation of caspase-3 and caspase-8, and initiation of poly (ADP) ribose polymerase (PARP) cleavage.
Casp8↑,
cl‑PARP↑,
eff↑, AKBA was preincubated with LY294002 or wortmannin (inhibitors of PI3K), it caused a significant enhancement of apoptosis in HT-29 cells
chemoPv↑, chemopreventive response of AKBA was estimated against intestinal adenomatous polyposis through the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
ascitic↓, AKBA by the suppression of ascites,
Let-7↑, AKBA could up-regulate the expression of let-7 and miR-200
miR-200b↑,
eff↑, anti-tumorigenic effects of curcumin and AKBA on the regulation of specific cancer-related miRNAs in colorectal cancer cells, and confirmed their protective action
MMP1↓, . It can inhibit the expression of MMP-1, MMP-2, and MMP-9 mRNAs along with secretions of TNF-α and IL-1β in THP-1 cells.
MMP2↓,
eff↑, combined administration of metformin, an anti-diabetic drug, and boswellic acid nanoparticles exhibited significant synergism through the inhibition of MiaPaCa-2 pancreatic cancer cell proliferation
BioAv↓, BA as a therapeutic drug is its poor bioavailability
BioAv↑, administration of BSE-018 concomitantly with a high-fat meal led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA)
Half-Life↓, drug needs to be given orally at the interval of six hours due to its calculated half- life, which was around 6 hrs.
toxicity↓, BSE has been found to be a safe drug without any adverse side reactions, and is well tolerated on oral administration.
Dose↑, Boswellia serrata extract to the maximum amount of 4200 mg/day is not toxic and it is safe to use though it shows poor bioavailability
BioAv↑, Approaches like lecithin delivery form (Phytosome®), nanoparticle delivery systems like liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly (lactic-co-glycolic acid) nanoparticles
ChemoSen↑, Like any other natural products BA can also be effective as chemosensitizer

5897- CAR,    Carvacrol Selectively Induces Mitochondria-Related Apoptotic Signaling in Primary Breast Cancer-Associated Fibroblasts
- in-vitro, BC, NA
Bax:Bcl2↑, marked increase in the BAX/BCL-XL ratio
PPARα↓, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3
NF-kB↓,
SIRT1↑,
SIRT3↑,
MMP3↓,
selectivity↑, Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts.
Bcl-2↓, In breast cancer lines, CV has been reported to down-regulate Bcl-2, up-regulate Bax, and induce caspase-3/-6/-9 activation in a dose-dependent manner, consistent with mitochondrial apoptosis
BAX↑,
Casp3↑,
Casp6↑,
Casp9↑,
mt-Apoptosis↑,

2785- CHr,    Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin
- Review, Var, NA
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

3238- EGCG,    Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications
- Review, Var, NA
Telomerase↓, EGCG stimulates telomere fragmentation through inhibiting telomerase activity.
DNMTs↓, EGCG reduced DNMTs,
cycD1/CCND1↓, EGCG also reduced the protein expression of cyclin D1, cyclin E, CDK2, CDK4, and CDK6. EGCG also inhibited the activity of CDK2 and CDK4, and caused Rb hypophosphorylation
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
HATs↓, EGCG can inhibit certain biomedically important molecular targets such as DNMTs, HATs, and HDACs
HDAC↓,
selectivity↑, EGCG has shown higher cytotoxicity in cancer cells than in their normal counterparts.
uPA↓, EGCG blocks urokinase, an enzyme which is essential for cancer growth and metastasis
NF-kB↓, EGCG inhibits NFκB and expression of TNF-α, reduces cancer promotion
TNF-α↓,
*ROS↓, It acts as strong ROS scavenger and antioxidant,
*antiOx↑,
Hif1a↓, ↓ HIF-1α; ↓ VEGF; ↓ VEGFR1;
VEGF↓,
MMP2↓, ↓ MMP-2; ↓ MMP-9; ↓ FAK;
MMP9↓,
FAK↓,
TIMP2↑, TIMP-2; ↑
Mcl-1↓, ↓ Mcl-1; ↓ survivin; ↓ XIAP
survivin↓,
XIAP↓,
PCNA↓, ↓ PCNA; ↑ 16; ↑ p18; ↑ p21; ↑ p27; ↑ pRb; ↑ p53; ↑ mdm2
p16↑,
P21↑,
p27↑,
pRB↑,
P53↑,
MDM2↑,
ROS↑, ↑ ROS; ↑ caspase-3; ↑ caspase-8; ↑ caspase-9; ↑ cytochrome c; ↑ Smac/DIABLO; ↓↑ Bax; Z Bak; ↓ cleaved PPAR;
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑,
Diablo↑,
BAX⇅,
cl‑PPARα↓,
PDGF↓, ↓ PDGF; ↓ PDGFRb; ↓ EGFR;
EGFR↓,
FOXO↑, activated FOXO transcription factors
AP-1↓, The inhibition of AP-1 activity by EGCG was associated with inhibition of JNK activation but not ERK activation.
JNK↓,
COX2↓, EGCG reduces the activity of COX-2 following interleukin-1A stimulation of human chondrocytes
angioG↓, EGCG inhibits angiogenesis by enhancing FOXO transcriptional activity


Showing Research Papers: 1 to 4 of 4

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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↓, 1,   lipid-P?, 1,   lipid-P↑, 1,   NRF2↓, 1,   ROS↑, 2,   SIRT3↑, 1,  

Metal & Cofactor Biology ⓘ

Tf↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   HK2↓, 1,   LDH↓, 1,   LDL↓, 1,   PDK1↓, 1,   PPARα↓, 3,   cl‑PPARα↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   mt-Apoptosis↑, 1,   BAX↑, 1,   BAX⇅, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 4,   Casp6↑, 1,   Casp8↑, 2,   Casp9↑, 2,   Cyt‑c↑, 2,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 1,   hTERT/TERT↓, 1,   iNOS↓, 1,   JNK↓, 1,   Mcl-1↓, 2,   MDM2↑, 1,   p27↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

HATs↓, 1,   pRB↑, 1,  

Protein Folding & ER Stress ⓘ

p‑eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,   XBP-1↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMTs↓, 1,   p16↑, 1,   P53↑, 1,   PARP↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 2,   P21↑, 1,   p‑RB1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   p‑ERK↓, 1,   FOXO↑, 1,   HDAC↓, 2,   Let-7↑, 1,   mTOR↓, 1,   NOTCH1↑, 1,   STAT3↓, 2,   TOP1↓, 2,   TOP2↑, 1,   Wnt↓, 1,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 1,   CLDN1↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   Fibronectin↓, 1,   miR-200b↑, 1,   MMP-10↓, 1,   MMP1↓, 1,   MMP2↓, 3,   MMP3↓, 1,   MMP9↓, 3,   PDGF↓, 2,   Slug↓, 1,   Snail↓, 1,   TET1↑, 1,   TIMP2↑, 1,   TumCI↓, 1,   Twist↓, 1,   uPA↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 2,   Hif1a↓, 2,   p‑PDGFR-BB↓, 1,   VEGF↓, 4,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   COX2↑, 1,   CXCR4↓, 1,   IKKα↓, 1,   IL10↓, 1,   IL1α↓, 1,   IL1β↓, 1,   IL6↓, 1,   MCP1↓, 1,   MIP2↓, 1,   NF-kB↓, 3,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

5HT↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   ChemoSen↑, 1,   Dose↑, 1,   eff↑, 6,   Half-Life↓, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AR↓, 1,   ascitic↓, 1,   EGFR↓, 2,   hTERT/TERT↓, 1,   IL6↓, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoPv↑, 1,   neuroP↑, 1,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 137

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,  

Cell Death ⓘ

iNOS↓, 1,   MAPK↑, 1,  

Migration ⓘ

Ca+2↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

AST↓, 1,  
Total Targets: 10

Scientific Paper Hit Count for: PPARα, Peroxisome Proliferator-Activated Receptor Alpha
1 Boswellia (frankincense)
1 Carvacrol
1 Chrysin
1 EGCG (Epigallocatechin Gallate)
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

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