Piperine / STAT3 Cancer Research Results

PI, Piperine: Click to Expand ⟱
Features:
Compound of black pepper that boosts bioavailability of curcumin

piperine’s bioenhancing function, often more important than piperine’s direct anticancer activity 
Mechanisms of bioenhancement
| Mechanism                     | Effect                             |
| ----------------------------- | ---------------------------------- |
| **↓ CYP3A4, CYP2C9**          | Slows metabolic clearance          |
| **↓ UGT (glucuronidation)**   | Increases parent compound exposure |
| **↓ P-glycoprotein (ABCB1)**  | Improves intracellular retention   |
| **↑ Intestinal permeability** | Better oral absorption             |

-Curcumin: ↑ bioavailability ~20–30×
-Resveratrol, EGCG, quercetin: ↑ exposure 2–10×

Primary pathways: NF-κB, STAT3, PI3K/Akt/mTOR, apoptosis, EMT
Direct anticancer potency: modest
Bioenhancing value: central and often dominant
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Wnt / β-catenin signaling ↓ Wnt/β-catenin (↓ β-catenin nuclear program) Growth & stemness suppression Piperine suppresses canonical Wnt signaling and shows anti-cancer effects in colorectal cancer cells (ref)
2 PI3K → AKT survival signaling ↓ PI3K/AKT signaling Reduced survival / increased apoptosis Gastric cancer study concludes piperine inhibits proliferation and induces apoptosis through inhibition of PI3K/Akt signaling (ref)
3 AKT → mTOR axis ↓ Akt/mTOR Anti-growth + anti-migration Piperine downregulates Akt/mTOR signaling with associated inhibition of migration and MMP-9 expression (ref)
4 NF-κB transcriptional program ↓ NF-κB activation Reduced inflammatory / pro-survival gene expression Piperine is reported as a potent inhibitor of NF-κB and related transcription factor activity in melanoma cells (ref)
5 STAT3 → Snail EMT axis ↓ STAT3 / ↓ Snail → ↓ EMT Anti-migration / anti-invasion Piperine inhibits colorectal cancer migration/invasion through a STAT3/Snail-mediated EMT mechanism (ref)
6 Multidrug resistance transporter ABCB1 (P-gp) ↓ P-gp-mediated efflux (chemosensitization) Improved chemo response (MDR reversal) Demonstrates piperine has chemosensitizing activity in P-gp–mediated MDR models (piperine characterized as P-gp substrate/modulator) (ref)
7 ROS / oxidative stress ↑ ROS Upstream stress trigger Piperine induces oxidative stress in cancer cells (ROS increase shown) and links it to growth inhibition/apoptosis (ref)
8 Intrinsic apoptosis (caspase activation) ↑ apoptosis Programmed cell death HeLa study: piperine induces apoptosis in a dose-dependent manner with apoptosis markers reported (ref)
9 Autophagy-dependent cell death (ROS–Akt/mTOR coupling) ↑ autophagy-dependent death (with ↓ Akt/mTOR) Stress-lethal program Colon cancer study: piperine induces autophagy-dependent cell death by increasing ROS and inhibiting Akt/mTOR signaling (ref)
10 Cell-cycle progression ↑ cell-cycle arrest (context-dependent) Proliferation blockade Rectal cancer cell study: piperine impairs cell-cycle progression and produces cytostatic/cytotoxic effects (ref)
11 Migration / invasion (MMP-9 axis) ↓ migration / ↓ MMP-9 Anti-metastatic phenotype Piperine suppresses migration with MMP-9 downregulation and Akt/mTOR inhibition (ref)
12 In vivo chemosensitization (doxorubicin) ↑ doxorubicin sensitivity Enhanced therapeutic efficacy Study evaluates piperine as an adjuvant to enhance doxorubicin sensitivity in triple-negative breast cancer models (ref)


STAT3, Signal transducer and activator of transcription 3: Click to Expand ⟱
Source:
Type: Oncogene
Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response.
Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.)

-STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors.
-Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).
Scientific Papers found: Click to Expand⟱
3597- PI,    Chronic diseases, inflammation, and spices: how are they linked?
- Review, AD, NA - Review, Park, NA - Review, Var, NA
*NF-kB↓, *MAPK↓, *AP-1↓, *COX2↓, *NOS2↓, *IL1β↓, *TNF-α↓, *PGE2↓, *STAT3↓, *IL10↑, *IL4↓, *IL5↓, P53↑, MMP9↓, MMP2↓, cMyc↓, VEGF↓, STAT3↓, survivin↓, p65↓,
5211- PI,    Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial-mesenchymal transition
- in-vitro, CRC, NA
TumCMig↓, TumCI↓, EMT↓, Snail↓, STAT3↓,
1165- PI,    Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells
- in-vitro, GC, TMK-1
p38↓, IL6↓, STAT3↓,
1254- PI,  VitC,    Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathway
- in-vivo, GC, NA
STAT3⇅, eff↑, ROS↑, Apoptosis↑,

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 ⓘ

ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   p38↓, 1,   survivin↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   STAT3↓, 3,   STAT3⇅, 1,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   Snail↓, 1,   TumCI↓, 1,   TumCMig↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL6↓, 1,   p65↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  
Total Targets: 19

Pathway results for Effect on Normal Cells:


Cell Death ⓘ

MAPK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

STAT3↓, 1,  

Migration ⓘ

AP-1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL10↑, 1,   IL1β↓, 1,   IL4↓, 1,   IL5↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

NOS2↓, 1,  
Total Targets: 12

Scientific Paper Hit Count for: STAT3, Signal transducer and activator of transcription 3
4 Piperine
1 Vitamin C (Ascorbic Acid)
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:133  Target#:373  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page