Piperlongumine / TumCI Cancer Research Results

PL, Piperlongumine: Click to Expand ⟱
Features:
Piperlongumine (also called Piplartine), an alkaloid from long pepper fruit
-Piperlongumine is a bioactive alkaloid derived from the long pepper (Piper longum)
– Piperlongumine has been shown to selectively increase ROS levels in cancer cells.
-NLRP3 inhibitor?
-TrxR inhibitor (major antioxidant system) to increase ROS in cancer cells
-ic50 cancer cells maybe 2-10uM, normal cells maybe exceeding 20uM.

Available from mcsformulas.com
-(Long Pepper, 500mg/Capsule)- 1 capsule 3 times daily with food
-Piperlongumine Pro Liposomal, 40 mg-take 1 capsule daily with plenty of water, after a meal

-Note half-life 30–60 minutes
BioAv poor aqueous solubility and bioavailability
Pathways:
- induce ROS production in cancer cells likely at any dose. Effect on normal cells is inconclusive.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, Prx,
- Lowers some AntiOxidant markers/ defense in Cancer Cells: but mostly raises NRF2 (raises antiO defense), TrxR↓(*important), GSH↓ Catalase↓ HO1↓ GPx↓
- Very little indication of raising AntiOxidant defense in Normal Cells: GSH↑,
- lowers Inflammation : NF-kB↓, COX2↓, conversely p38↑, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, VEGF↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓(few reports), DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓,
- small indication of inhibiting glycolysis : HIF-1α↓, cMyc↓, LDH↓, HK2↓,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, ERK↓, JNK,
- Synergies: chemo-sensitization, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Transformation-linked oxidative stress dependence ↑ ROS Cancer-selective stress overload Landmark study: piperlongumine selectively kills cells with a cancer genotype by elevating ROS; antioxidant rescue blocks killing (ref)
2 GSTP1 redox buffering (glutathione S-transferase π) ↓ GSTP1 function / ↑ ROS Disables antioxidant buffering Biochemical/structural work describing GSTP1 as a piperlongumine target and linking PL exposure to increased ROS and decreased GSH (ref)
3 ER stress / UPR via PRDX4 (Peroxiredoxin 4) ↓ PRDX4 activity / ↑ ER stress Proteotoxic stress, preferential glioma killing Piperlongumine inactivates PRDX4, exacerbates ER stress, increases ROS, and preferentially kills high-grade glioma cells (ref)
4 Mitochondrial disruption + stress MAPK (JNK) ↓ ΔΨm / ↑ JNK Mitochondrial apoptosis signaling Example mechanistic paper: piperlongumine induces ROS-mediated mitochondrial disruption and activates JNK associated with apoptosis (ref)
5 DNA damage response ↑ DNA damage Checkpoint activation, death signaling Piperlongumine elevates ROS and causes DNA damage in pancreatic cancer models; antioxidant reverses DNA damage and killing (ref)
6 STAT3 signaling ↓ STAT3 activity (↓ pSTAT3 / ↓ STAT3 function) Reduced survival & stem-like growth Drug-repositioning study identifies piperlongumine as a direct STAT3 inhibitor; shows reduced STAT3 activation and mammosphere inhibition (ref)
7 NF-κB signaling ↓ NF-κB DNA binding / ↓ nuclear translocation Reduced inflammatory & anti-apoptotic transcription Piperlongumine down-regulates NF-κB DNA-binding activity and decreases nuclear translocation of p50/p65 in prostate cancer cells (ref)
8 PI3K–AKT–mTOR pathway ↓ PI3K/AKT/mTOR signaling Growth suppression; promotes apoptosis/autophagy Paper explicitly reporting piperlongumine induces apoptosis and autophagy through inhibition of PI3K/Akt/mTOR in lung cancer cells (ref)
9 p38 signaling (stress kinase) ↑ p38 signaling Stress response; autophagy involvement Mechanistic study showing piperlongumine induces autophagy by targeting p38 signaling (ref)
10 Cell cycle regulation ↑ G2/M arrest Proliferation block Demonstrates piperlongumine induces G2/M cell-cycle arrest in MCF-7 cells (cell cycle distribution shift shown) (ref)
11 EMT / migration / invasion ↓ EMT / ↓ migration & invasion Anti-metastatic phenotype Reports piperlongumine inhibits TGF-β–induced EMT and reduces migration/invasion in cancer cells (ref)
12 Ferroptosis (iron-dependent oxidative death) ↑ ferroptosis Non-apoptotic killing modality Shows piperlongumine-induced cancer cell death is inhibited by ferroptosis inhibitors and iron chelation, supporting ferroptosis involvement (ref)


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
2952- PL,    Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization
- in-vitro, Bladder, T24/HTB-9 - in-vivo, Bladder, NA
TumCP↓, TumCCA↑, TumCMig↓, TumCI↓, ROS↑, Slug↓, β-catenin/ZEB1↓, Zeb1↓, N-cadherin↓, F-actin↓, GSH↓, EMT↓, CLDN1↓, ZO-1↓,
2961- PL,    Piperlongumine inhibits esophageal squamous cell carcinoma in vitro and in vivo by triggering NRF2/ROS/TXNIP/NLRP3-dependent pyroptosis
- in-vitro, ESCC, KYSE-30
Pyro↑, TumCP↓, TumCMig↓, TumCI↓, ASC↑, cl‑Casp1↑, NLRP3↑, GSDMD↑, ROS↑, NRF2↓, TXNIP↑,
2950- PL,    Overview of piperlongumine analogues and their therapeutic potential
- Review, Var, NA
AntiAg↑, neuroP↑, Inflam↓, NO↓, PGE2↓, MMP3↓, MMP13↓, TumCMig↓, TumCI↓, p38↑, JNK↑, NF-kB↑, ROS↑, FOXM1↓, TrxR1↓, GSH↓, Trx↓, cMyc↓, Casp3↑, Bcl-2↓, Mcl-1↓, STAT3↓, AR↓, DNAdam↑,
1939- PL,    Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP
- in-vitro, HCC, HepG2 - in-vitro, HCC, HUH7 - in-vivo, NA, NA
TumCMig↓, TumCI↓, ER Stress↑, selectivity↑, tumCV↓, ROS↑, GSH↓, eff↓, Ca+2↑, MAPK↑, CHOP↑, Dose↝,
2946- PL,    Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent
- Review, Var, NA
ROS↑, GSH↓, DNAdam↑, ChemoSen↑, RadioS↑, BioEnh↑, selectivity↑, BioAv↓, eff↑, p‑Akt↓, mTOR↓, GSK‐3β↓, β-catenin/ZEB1↓, HK2↓, Glycolysis↓, Cyt‑c↑, Casp9↑, Casp3↑, Casp7↑, cl‑PARP↑, TrxR↓, ER Stress↑, ATF4↝, CHOP↑, Prx4↑, NF-kB↓, cycD1/CCND1↓, CDK4↓, CDK6↓, p‑RB1↓, RAS↓, cMyc↓, TumCCA↑, selectivity↑, STAT3↓, NRF2↑, HO-1↑, PTEN↑, P-gp↓, MDR1↓, MRP1↓, survivin↓, Twist↓, AP-1↓, Sp1/3/4↓, STAT1↓, STAT6↓, SOX4↑, XBP-1↑, P21↑, eff↑, Inflam↓, COX2↓, IL6↓, MMP9↓, TumMeta↓, TumCI↓, ICAM-1↓, CXCR4↓, VEGF↓, angioG↓, Half-Life↝, BioAv↑,
2948- PL,    The promising potential of piperlongumine as an emerging therapeutics for cancer
- Review, Var, NA
tumCV↓, TumCP↓, TumCI↓, angioG↓, EMT↓, TumMeta↓, *hepatoP↑, *lipid-P↓, *GSH↑, cardioP↑, CycB/CCNB1↓, cycD1/CCND1↓, CDK2↓, CDK1↓, CDK4↓, CDK6↓, PCNA↓, Akt↓, mTOR↓, Glycolysis↓, NF-kB↓, IKKα↓, JAK1↓, JAK2↓, STAT3↓, ERK↓, cFos↓, Slug↓, E-cadherin↑, TOP2↓, P53↑, P21↑, Bcl-2↓, BAX↑, Casp3↑, Casp7↑, Casp8↑, p‑HER2/EBBR2↓, HO-1↑, NRF2↑, BIM↑, p‑FOXO3↓, Sp1/3/4↓, cMyc↓, EGFR↓, survivin↓, cMET↓, NQO1↑, SOD2↑, TrxR↓, MDM2↓, p‑eIF2α↑, ATF4↑, CHOP↑, MDA↑, Ki-67↓, MMP9↓, Twist↓, SOX2↓, Nanog↓, OCT4↓, N-cadherin↓, Vim↓, Snail↓, TumW↓, TumCG↓, HK2↓, RB1↓, IL6↓, IL8↓, SOD1↑, RadioS↑, ChemoSen↑, toxicity↓, Sp1/3/4↓, GSH↓, SOD↑,

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 ⓘ

GSH↓, 5,   HO-1↑, 2,   MDA↑, 1,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 2,   Prx4↑, 1,   ROS↑, 5,   SOD↑, 1,   SOD1↑, 1,   SOD2↑, 1,   Trx↓, 1,   TrxR↓, 2,   TrxR1↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   Glycolysis↓, 2,   HK2↓, 2,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   BAX↑, 1,   Bcl-2↓, 2,   BIM↑, 1,   cl‑Casp1↑, 1,   Casp3↑, 3,   Casp7↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   GSDMD↑, 1,   JNK↑, 1,   MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   p38↑, 1,   Pyro↑, 1,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

p‑HER2/EBBR2↓, 1,   Sp1/3/4↓, 3,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   p‑eIF2α↑, 1,   ER Stress↑, 2,   XBP-1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   CDK4↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   P21↑, 2,   RB1↓, 1,   p‑RB1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   cMET↓, 1,   EMT↓, 2,   ERK↓, 1,   FOXM1↓, 1,   p‑FOXO3↓, 1,   GSK‐3β↓, 1,   mTOR↓, 2,   Nanog↓, 1,   OCT4↓, 1,   PTEN↑, 1,   RAS↓, 1,   SOX2↓, 1,   STAT1↓, 1,   STAT3↓, 3,   STAT6↓, 1,   TOP2↓, 1,   TumCG↓, 1,  

Migration ⓘ

AntiAg↑, 1,   AP-1↓, 1,   Ca+2↑, 1,   CLDN1↓, 1,   E-cadherin↑, 1,   F-actin↓, 1,   Ki-67↓, 1,   MMP13↓, 1,   MMP3↓, 1,   MMP9↓, 2,   N-cadherin↓, 2,   Slug↓, 2,   Snail↓, 1,   SOX4↑, 1,   TumCI↓, 6,   TumCMig↓, 4,   TumCP↓, 3,   TumMeta↓, 2,   Twist↓, 2,   TXNIP↑, 1,   Vim↓, 1,   Zeb1↓, 1,   ZO-1↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↑, 1,   ATF4↝, 1,   EGFR↓, 1,   NO↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↑, 1,   COX2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IKKα↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 2,   JAK1↓, 1,   JAK2↓, 1,   NF-kB↓, 2,   NF-kB↑, 1,   PGE2↓, 1,  

Protein Aggregation ⓘ

NLRP3↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioEnh↑, 1,   ChemoSen↑, 2,   Dose↝, 1,   eff↓, 1,   eff↑, 2,   Half-Life↝, 1,   MDR1↓, 1,   MRP1↓, 1,   RadioS↑, 2,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   FOXM1↓, 1,   p‑HER2/EBBR2↓, 1,   IL6↓, 2,   Ki-67↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   neuroP↑, 1,   toxicity↓, 1,   TumW↓, 1,  
Total Targets: 143

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

GSH↑, 1,   lipid-P↓, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
6 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#:134  Target#:324  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page