Piperine / mTOR 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)


mTOR, mammalian target of rapamycin: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
mTOR (mechanistic target of rapamycin) is a central regulator of cell growth, proliferation, metabolism, and survival. It is a serine/threonine kinase that integrates signals from nutrients, growth factors, and cellular energy status.
mTOR promotes protein synthesis and cell growth by activating downstream targets such as S6 kinase and 4E-BP1. In cancer, this pathway can become hyperactivated, leading to uncontrolled cell proliferation.

mTor Inhibitors:
-rapamycin (Sirolimus): classic natural product mTOR inhibitor
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
-Honokiol
Scientific Papers found: Click to Expand⟱
5209- PI,    Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP-9 signaling pathway in DU145 cells
- in-vitro, Pca, DU145
TumCP↓, data revealed that piperine markedly repressed cell proliferation and migration, and induced apoptosis in PCa DU145.
TumCMig↓,
Apoptosis↑,
p‑Akt↓, piperine reduced the expression of p-Akt, MMP-9 and p-mTOR.
MMP9↓,
p‑mTOR↓,
TumMeta↓, therapeutic agent to better overcome PCa metastasis
*antiOx↓, piperine has an extensive pharmacological properties, such as antioxidant (7), anti-inflammatory (8,9), hepatoprotective (10), antimicrobial (11,12), immunomodulatory and anticancer
*Inflam↓,
*hepatoP↑,
*Imm↑,
*AntiCan↑,

5214- PI,    Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS production
- vitro+vivo, CRC, HCT116 - in-vitro, CRC, SW48 - in-vitro, CRC, SW-620
TumCP↓, Piperine inhibits colorectal cancer (CRC) cells proliferation both in vitro and in CRC xenograft mouse model.
TumAuto↑, Piperine inhibits CRC cells growth by promoting autophagic cell death.
Akt↓, Piperine induces autophagy by repressing the Akt/mTOR pathway in CRC cells.
mTOR↓,
ROS↑, Piperine induces ROS production in CRC cells.

5216- PI,  doxoR,    Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cells
- vitro+vivo, BC, MDA-MB-231
ChemoSen↑, synergistic interaction between DOX and PIP on MDA-MB-231 cells.
necrosis↑, combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities.
PTEN↓,
PI3K↓,
p‑Akt↓,
mTOR↓,
ALDH↓,
TumVol↓, Combining PIP to DOX reduces tumor size and improves survival of tumor-bearing mice
OS↑, combining PIP to DOX improved survival rates in mice compared to their DOX-treated counterparts (Fig. 4B).
cardioP↑, PIP protects against DOX-induced cardiotoxicity
cl‑PARP↑, PIP enhances apoptosis via PARP cleavage in EAC-tumor bearing mice

1946- PL,  PI,    Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling
- in-vitro, Liver, NA
eff↑, Among these, compound 9m exerted the most potent antiproliferative activity against drug-resistant Bel-7402/5-FU human liver cancer 5-FU resistant cells (IC50 = 0.8 μM), which was approximately 10-fold lower than piperlongumine (IC50 = 8.4 μM).
toxicity↓, Further, 9m showed considerably lower cytotoxicity against LO2 human normal liver epithelial cells compared to Bel-7402/5-FU.
TrxR↓, Mechanistically, compound 9m inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, reduced mitochondrial transmembrane potential (MTP
ROS↑,
MMP↓,
p38↑, Finally, 9m activated significantly the p38 signaling pathways and suppressed the Akt/mTOR signaling pathways.
Akt↓,
mTOR↓,


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(tgid=1) ⓘ

ROS↑, 2,   TrxR↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   necrosis↑, 1,   p38↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 2,   p‑Akt↓, 2,   mTOR↓, 3,   p‑mTOR↓, 1,   PI3K↓, 1,   PTEN↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

cl‑PARP↑, 1,  

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

ALDH↓, 1,   TumCP↓, 2,  

Migration(tgid=13) ⓘ

MMP9↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,  

Barriers & Transport(tgid=15) ⓘ

MMP↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 1,   OS↑, 1,   toxicity↓, 1,   TumVol↓, 1,  
Total Targets: 25

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1,   Inflam↓, 1,  

Functional Outcomes(tgid=23) ⓘ

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

Scientific Paper Hit Count for: mTOR, mammalian target of rapamycin
4 Piperine
1 doxorubicin
1 Piperlongumine
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#:209  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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