TRIB3 Cancer Research Results

TRIB3, tribbles homolog 3: Click to Expand ⟱
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TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors.
TRIB3 encodes a pseudokinase—a kinase-like protein lacking catalytic activity but acting as a scaffold and signaling modulator. TRIB3 is strongly induced by cellular stress, particularly ER stress, nutrient deprivation, hypoxia, and oxidative stress, via ATF4/CHOP-dependent pathways.
Functionally UPREGULATED in many cancers, particularly in aggressive, hypoxic, or metabolically stressed tumors.
-Rarely mutated
-Induced by the tumor microenvironment
-Maintained by chronic stress signaling

TRIB3 is best viewed as a stress-selected dependency, not a classical oncogene.

High TRIB3 expression correlates with:
-EMT and invasive behavior
-Metastatic competence
-Poor prognosis in multiple solid tumors (e.g., breast, lung, colorectal, liver)

TRIB3 reports whether a tumor has entered a stress-adapted, survival-biased state. It is not used to choose a specific drug today.
TRIB3 is used as a clinical biomarker for Stress Adaptation


Scientific Papers found: Click to Expand⟱
5858- CAP,    Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
- Review, Nor, NA - Review, AD, NA
*BBB↓, crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition.
*GutMicro↑, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. often favoring the growth of beneficial taxa such as Ruminococcaceae, Lac
Obesity↓, These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects
*Inflam↓,
*AntiCan↑,
*TRPV1↑, Capsaicin is a potent agonist perceived by TRPV1, a transmembrane cation channel that functions with Ca2+.
*Ca+2↑, causes an increase in Ca2+ flux,
*antiOx↑, Capsaicin is a bioactive compound of chili peppers responsible for their spicy flavor, which also shows antioxidant, anti-obesity, analgesic, anti-inflammatory, anticarcinogenic, and cardioprotective effects
*cardioP↑,
*BioAv↓, capsaicin exhibits low systemic bioavailability due to its rapid metabolism in the liver and other tissues, resulting in a short plasma half-life of approximately 25 min in humans
*Half-Life↓,
*BioAv↝, Capsaicin’s bioavailability is determined by multiple interrelated factors, including its physicochemical properties, metabolic transformations, route of administration, and the biological context of the host, including gut microbiota composition.
*BioAv↑, For instance, polymeric micelles, liposomes, and hydroxypropyl-β-cyclodextrin complexes have demonstrated the capacity to enhance capsaicin’s oral bioavailability, prolong its plasma half-life, and improve therapeutic consistency
*neuroP↑, capsaicin exposure alters glutamate, GABA, and serotonin levels in distinct brain regions, with potential implications for neuroprotection, mood regulation, and energy metabolism.
Apoptosis↑, apoptosis is the main mechanism by which capsaicin induces cell death in cancer cells.
p38↑, capsaicin triggers a calcium flux within the cell via TRPV1, activating the p38 pathway.
ROS↑, As a result, reactive oxygen species (ROS) are produced, along with depolarization of the mitochondrial membrane potential and opening of the mitochondrial permeability transition pore.
MMP↓,
MPT↑,
Cyt‑c↑, Consequently, cytochrome c is released, the apoptosome is assembled, and caspases are activated, ultimately leading to cell death
Casp↑,
TRIB3↑, capsaicin enhances TRIB3 gene expression, which allowed an increase in the antiproliferative and proapoptotic effects of TRIB3 in cancer cells
NADH↓, Capsaicin has also been seen to downregulate and inhibit tumor-associated NADH oxidase (tNOX) and Sirtuin1 (SIRT1) in multiple cancer cell lines such as bladder cancer, which led to reduced cell growth and migration
SIRT1↓,
TumCG↓,
TumCMig↓,
TOP1↓, pointing out that capsaicin had an inhibitory effect on topoisomerases I and II, causing a reduction in metabolic activity and proliferation of a human colon cancer cell line
TOP2↓,
β-catenin/ZEB1↓, with capsaicin, the β-catenin transcription gets downregulated
*ROS↓, Capsaicin has also been proven to alleviate redox imbalance or oxidative stress, thanks to its antioxidative activity.
*Aβ↓, Alsheimer’s disease, attenuating neurodegeneration in mice by reducing amyloid-beta levels via the promotion of non-amyloidogenic processing of amyloid precursor protein

6819- EMD,    Recent advances in the therapeutic potential of emodin for human health
- Review, Nor, NA
AntiCan↑, It has therapeutic effects in cancer, diabetes, neurodegenerative diseases or chronic inflammatory diseases.
*AntiDiabetic↑, anticancer, neuroprotective, antidiabetic, antioxidant and anti-inflammatory.
*neuroP↑,
*Inflam↓,
*antiOx↑,
*BioAv↓, Because its bioavailability is low, there are limitations in clinical therapeutic use.
*BioAv↑, combined administration of emodin and piperine has been observed to clinically improve emodin pharmacokinetics, increasing 221 % of the area under the curve (AUC), 258 % the maximum concentration (Cmax), and decreasing 230 % the clearance related to
*SOD↑, fig 2 antioxidant
*GPx↑,
*GSH↑,
*NRF2↑,
*ROS↓,
*lipid-P↓,
*Cyt‑c↓,
*BAX↓, fig 2 antiinflammatory
*Bcl-2↓,
*iNOS↓,
*NO↓,
*IL6↓,
*IL10↓,
*IL17↓,
*IFN-γ↓,
*NF-kB↓,
*LC3II↓,
*Akt↓,
*Beclin-1↓,
*AMPK↓, fig 2 neuroprotective
*TNF-α↓,
*PGE2↓,
*Apoptosis↓,
*Casp3↓,
*Casp9↓,
*P53↓,
*P21↓,
*NAD↓, neuronal oxidative stress
*ATP↓,
*CHOP↓,
*GADD34↓,
*ATF4↓,
tumCV↓, fig 2 anticancer
Apoptosis↑,
TumCG↓,
TumCI↓,
TumMeta↓,
CSCs↓, glioma stem cells ↓b-catenin, ↓Notch-1, ↓STAT3
NOTCH1↓,
STAT3↓,
eff↑, emodin combined with curcumin ↓proliferation, ↑miR-34a
miR-34a↓,
*neuroP↑, Neuroprotective LPS-stimulated mouse ↓Nrf-2, NQO1, ↓TNF-α,↓↓ IL-6, ↓NO, ↓PGE2
*BDNF↓, model of chronic stress mice in vivo ↓progression of behavioral impairments in mice ↓consumption of sucrose, ↓plasmatic corticosterone, ↓mRNA, ↓BDNF,
*hepatoP↑, Hepatoprotective rats in vivo ↓ethanol-mediated liver steatosis ↓ ALT, ↓AST, ↓ TGL
*ALAT↓,
*AST↓,
TG/TAG↓,
ROS↑, However, at higher concentrations, emodin significantly increased ROS generation and reduced cell viability.
Slug↓, expression levels of Slug (a transcription factor) were also suppressed with emodin treatment.
EMT↓, results suggested that emodin suppressed the epithelial-mesenchymal transition of cancer cells through the ILK/GSK-3β/Slug signaling pathway
Glycolysis↓, In addition, emodin inhibited glycolysis via ROS-induced inactivation of the PI3K/AKT signaling pathway.
ChemoSen↑, The study by Peng et al. [130] also showed chemosensitizing effects of emodin to cisplatin in A549 (2–20 µM, for 48 h) and H460 (0.5–10 µM) non-small cell lung cancer cells.
P-gp↓, The sensitization mechanism was mediated by the inhibition of P-glycoprotein (Pgp), a drug-resistant protein related to the efflux pump mechanism.
Ki-67↓, The significant reduction of Ki-67 and proliferating cell nuclear antigen (PCNA) protein levels supported the antiproliferative effect of emodin in animal models.
PCNA↓,
ER Stress↑, findings suggested that emodin exerts its apoptotic effects in a process mediated by ER stress and the activation of the TRIB3/NF-κB pathway in lung cancer cells.
TRIB3↑,
NF-kB↑,
TumMeta↑, Emodin (40 mg/kg for 7 days) significantly decreased the metastatic recurrence of breast cancer after surgery in the lungs by reducing the formation of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC).
*Imm↓, emodin may be developed as an immunosuppressive agent in case of immune activation, autoimmune disorders even in organ transplantation
*toxicity↝, An excess of emodin due to its laxative effects causes intestinal pain and severe diarrhea with subsequent electrolyte imbalance and dehydration [157]. Therefore, treatment should begin when symptoms appear, with special attention to electrolyte leve

150- NRF,  CUR,  docx,    Subverting ER-Stress towards Apoptosis by Nelfinavir and Curcumin Coexposure Augments Docetaxel Efficacy in Castration Resistant Prostate Cancer Cells
- in-vitro, Pca, C4-2B
p‑Akt↓,
p‑eIF2α↑, phosphorylated
ER Stress↑, Acute exposure (3–9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3.
ATF4↑, 3-drug combination rapidly enhances ER-stress associated death sensors, CHOP, ATF-4 and TRIB3 in C4-2B cells
CHOP↑,
TRIB3↑,
ChemoSen↑, subverting ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can chemosensitize the CRPC cells to DTX therapy.
Casp3↑, NFR or CUR alone could increase Caspase-3 activity in DTX exposed cells
cl‑PARP↑, PARP cleavage assays further confirmed this differential effect of drug combination on apoptotic cell death. In C4-2B cells, a 9-fold increase was observed
BID↑, 3-drug combination rapidly increases ER-stress transducers, BiP, eIF2µ and Xbp-1 in C4-2B cells
XBP-1↑,


Showing Research Papers: 1 to 3 of 3

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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

NADH↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,   MPT↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

p‑Akt↓, 1,   Apoptosis↑, 2,   BID↑, 1,   Casp↑, 1,   Casp3↑, 1,   Cyt‑c↑, 1,   p38↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 2,   XBP-1↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

cl‑PARP↑, 1,   PCNA↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,   EMT↓, 1,   miR-34a↓, 1,   NOTCH1↓, 1,   STAT3↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

Ki-67↓, 1,   Slug↓, 1,   TRIB3↑, 3,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   TumMeta↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↑, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

NF-kB↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 2,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

Ki-67↓, 1,   TG/TAG↓, 1,   TRIB3↑, 3,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   Obesity↓, 1,  
Total Targets: 46

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   GPx↑, 1,   GSH↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   AMPK↓, 1,   NAD↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↓, 1,   Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   GADD34↓, 1,   iNOS↓, 1,   TRPV1↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1,   LC3II↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,   NO↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IFN-γ↓, 1,   IL10↓, 1,   IL17↓, 1,   IL6↓, 1,   Imm↓, 1,   Inflam↓, 2,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

BDNF↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   cardioP↑, 1,   hepatoP↑, 1,   neuroP↑, 3,   toxicity↝, 1,  
Total Targets: 55

Scientific Paper Hit Count for: TRIB3, tribbles homolog 3
1 Capsaicin
1 Emodin
1 nelfinavir/Viracept
1 Curcumin
1 Docetaxel
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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