Piperine / Apoptosis 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)


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.
Scientific Papers found: Click to Expand⟱
5208- PI,    Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human Gastric Cancer Cells by Downregulating Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway
- in-vitro, GC, SNU16 - in-vitro, Nor, GES-1
TumCP↓, Apoptosis↑, BAX↑, BAD↑, Cyt‑c↑, cl‑PARP↑, cl‑Casp3↑, Bcl-2↓, Bcl-xL↓, p‑PI3K↓, p‑Akt↓, Ki-67↓, toxicity↓, RadioS↑,
5209- PI,    Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP-9 signaling pathway in DU145 cells
- in-vitro, Pca, DU145
TumCP↓, TumCMig↓, Apoptosis↑, p‑Akt↓, MMP9↓, p‑mTOR↓, TumMeta↓, *antiOx↓, *Inflam↓, *hepatoP↑, *Imm↑, *AntiCan↑,
5213- PI,    Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation
- in-vitro, Cerv, HeLa
Apoptosis↑, TumCG↓, ROS↑, MMP↓, DNAdam↑, Casp3↑, TumCCA↑, *Inflam↓, *antiOx↓, *hepatoP↑, ChemoSen↑, CSCs↓,
5215- PI,    Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells
- in-vitro, CRC, NA
TumCCA↑, Apoptosis↑, ROS↑, eff↓, BioEnh↑,
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↑,
1256- PI,    Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models
- in-vitro, adrenal, PHEO - in-vivo, NA, NA
Apoptosis↑, ROS↑, TumCMig↓, TumCI↓, EMT↓, angioG↓, Necroptosis↑, MAPK↑, ERK↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 4,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

p‑Akt↓, 2,   Apoptosis↑, 6,   BAD↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Cyt‑c↑, 1,   MAPK↑, 1,   Necroptosis↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   p‑mTOR↓, 1,   p‑PI3K↓, 1,   STAT3⇅, 1,   TumCG↓, 1,  

Migration ⓘ

Ki-67↓, 1,   MMP9↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,   ChemoSen↑, 1,   eff↓, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 37

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 2,  

Immune & Inflammatory Signaling ⓘ

Imm↑, 1,   Inflam↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   hepatoP↑, 2,  
Total Targets: 5

Scientific Paper Hit Count for: Apoptosis, Apoptosis
6 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#:14  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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