Piperine / NF-kB 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)


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
649- EGCG,  CUR,  PI,    Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
*BioEnh↑, EGFR↓, HER2/EBBR2↓, IGF-1↓, MAPK↓, ERK↓, RAS↓, Raf↓, NF-kB↓, p‑pRB↓, TumCCA↑, Glycolysis↓, Warburg↓, HK2↓, Pyruv↓,
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↓,
4220- PI,    Piperine ameliorated memory impairment and myelin damage in lysolecethin induced hippocampal demyelination
- in-vivo, AD, NA - in-vivo, MS, NA
*memory↑, *iNOS↓, *NRF2↑, *HO-1↑, *TAC↑, *TNF-α↓, *IL1β↓, *NF-kB↓, *IL10↑, *FOXP3↑, *BDNF↑, other↑,
5210- PI,    Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells
- in-vitro, Melanoma, B16-BL6
IL1β↓, TNF-α↓, MMPs↓, p65↓, p50↓, NF-kB↓, ATF2↓, cFos↓, CREB↓,
1016- PI,    Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cells
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW480 - in-vitro, CRC, DLD1
β-catenin/ZEB1↓, Wnt↓, TumCP↓, TumCMig↓, *antiOx↑, *Inflam↓, *hepatoP↑, *neuroP↑, *Bacteria↓, *memory↑, AntiCan↑, NF-kB↓, cFos↓, ATF2↓, CREB↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics ⓘ

Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   CREB↓, 2,   Glycolysis↓, 1,   HK2↓, 1,   Pyruv↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

ATF2↓, 2,   MAPK↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,   p‑pRB↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 2,   ERK↓, 1,   IGF-1↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   NF-kB↓, 3,   p50↓, 1,   p65↓, 2,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 37

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   TAC↑, 1,  

Cell Death ⓘ

iNOS↓, 1,   MAPK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

STAT3↓, 1,  

Migration ⓘ

AP-1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   FOXP3↑, 1,   IL10↑, 2,   IL1β↓, 2,   IL4↓, 1,   IL5↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,  

Clinical Biomarkers ⓘ

NOS2↓, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   memory↑, 2,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 25

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
5 Piperine
1 EGCG (Epigallocatechin Gallate)
1 Curcumin
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#:214  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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