Piperlongumine / eff 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)


eff, efficacy: Click to Expand ⟱
Source:
Type:
Power to enhance an anti cancer effect
Scientific Papers found: Click to Expand⟱
2964- PL,    Preformulation Studies on Piperlongumine
- Analysis, Nor, NA
*BioAv↓, *BioAv↑, *other↝, *eff↓,
2951- PL,  AF,    Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells
- in-vitro, GBM, U87MG
GSH↓, eff↑, GSTP1/GSTπ↓,
2953- PL,    Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation
- in-vitro, Nor, NA
*ROS↑, *GSTA1↓, eff↝, *toxicity↓, ROS↑, *Hif1a↓,
2956- PL,    Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis
- in-vitro, PC, NA
ROS↑, Ferroptosis↓, GSH↓, GPx↓, cl‑PARP∅, cl‑Casp3∅, eff↑, eff↑,
2957- PL,    Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKβ Suppression in Human Breast Cancer Cells
- in-vitro, BC, MCF-7
TumCP↓, TumCMig↓, TumCCA↑, ROS↑, H2O2↑, GSH↓, IKKα↓, NF-kB↓, P21↑, eff↓,
2958- PL,    Natural product piperlongumine inhibits proliferation of oral squamous carcinoma cells by inducing ferroptosis and inhibiting intracellular antioxidant capacity
- in-vitro, Oral, HSC3
TumCP↓, lipid-P↑, ROS↑, DNMT1↑, FTH1↓, GPx4↓, eff↓, GSH↓, Ferroptosis↑, MDA↓,
2962- PL,    Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2‑Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents
- in-vitro, Nor, PC12
*GSH↑, *NQO1↑, *Trx↑, *TrxR↑, *NRF2↑, *NRF2⇅, *eff↑, *BioAv↑, *ROS↓,
2965- PL,  docx,    Piperlongumine for enhancing oral bioavailability and cytotoxicity of docetaxel in triple negative breast cancer
- Analysis, Var, NA
BioEnh↑, eff↑,
2966- PL,    A strategy to improve the solubility and bioavailability of the insoluble drug piperlongumine through albumin nanoparticles
- in-vitro, LiverDam, NA
*Half-Life↑, *BioAv↑, eff↑, ROS↑,
2968- PL,  Chit,    efficient_cancer_therapy">Preparation of piperlongumine-loaded chitosan nanoparticles for safe and efficient cancer therapy
- in-vitro, GC, AGS
eff↑, Dose↝, ROS↑, BioAv↑,
1951- PL,    Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation
- in-vitro, Lung, A549
ROS↑, lipid-P↑, MMP↓, TumCCA↑, TrxR↓, eff↑,
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↝,
1940- PL,    Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
- in-vitro, GBM, LN229 - in-vitro, GBM, U87MG
ROS↑, GSH↓, p38↑, JNK↑, IKKα↑, NF-kB↓, eff↓,
1941- PL,    Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer
- in-vitro, HNSCC, NA
selectivity↑, eff↑, ROS↑, toxicity↑, GSH↓, GSSG↑, *GSSG∅, cl‑PARP↑, PUMA↑, GSTP1/GSTπ↓, ChemoSen↑,
1944- PL,    Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress
- in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2
ER Stress↑, TrxR1↓, ROS↑, eff↓, Bcl-2↓, proCasp3↓, BAX↓, cl‑Casp3↑, TumCCA↑, p‑PERK↑, ATF4↑, TumCG↓, lipid-P↑, selectivity↑,
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↑, toxicity↓, TrxR↓, ROS↑, MMP↓, p38↑, Akt↓, mTOR↓,
1947- PL,    Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer
- in-vitro, GC, SGC-7901 - in-vitro, GC, NA
TrxR1↓, ROS↑, ER Stress↑, mtDam↑, selectivity↑, NO↑, TumCCA↑, mt-ROS↑, Casp9↑, Bcl-2↓, Bcl-xL↓, cl‑PARP↑, eff↓, lipid-P↑,
1948- PL,  BNL,    Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy
- in-vitro, GBM, NA
selectivity↑, ROS↑, BioAv↓, BioAv↑, Apoptosis↑, TumCCA↑, eff↑,
1950- PL,    Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549
selectivity↑, ROS↑, SETBP1↓, cl‑Casp9↑, eff↓, FOSB↑,
1952- PL,  5-FU,    Piperlongumine induces ROS accumulation to reverse resistance of 5-FU in human colorectal cancer via targeting TrxR
- in-vivo, CRC, HCT8
ROS↑, TrxR↓, eff↑, p‑Akt↓,
2940- PL,    Piperlongumine Induces Reactive Oxygen Species (ROS)-dependent Downregulation of Specificity Protein Transcription Factors
- in-vitro, PC, PANC1 - in-vitro, Lung, A549 - in-vitro, Kidney, 786-O - in-vitro, BC, SkBr3
ROS↑, TumCP↓, Apoptosis↑, eff↓, Sp1/3/4↓, cycD1/CCND1↓, survivin↓, cMyc↓, EGFR↓, cMET↓,
2943- PL,    Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin
- in-vitro, CRC, HCT116 - in-vitro, Lung, A549 - in-vitro, BC, MCF-7
TrxR1?, TumCD↑, ROS↑, GSH↓, eff↑,
2944- PL,    Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells
- in-vitro, Thyroid, IHH4 - in-vitro, Thyroid, 8505C - in-vivo, NA, NA
ROS↑, selectivity↑, tumCV↓, TumCCA↑, Apoptosis↑, ERK↑, Akt↓, mTOR↓, neuroP↑, Bcl-2↓, Casp3↑, PARP↑, JNK↑, *toxicity↓, eff↓, TumW↓,
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↑,
2949- PL,    Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation
- in-vitro, GBM, LN229 - in-vitro, GBM, U87MG
selectivity↑, ROS↑, JNK↑, p38↑, GSH↓, eff↓,

Showing Research Papers: 1 to 25 of 25

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↓, 1,   Ferroptosis↑, 1,   GPx↓, 1,   GPx4↓, 1,   GSH↓, 10,   GSSG↑, 1,   GSTP1/GSTπ↓, 2,   H2O2↑, 1,   HO-1↑, 1,   lipid-P↑, 4,   MDA↓, 1,   NRF2↑, 1,   Prx4↑, 1,   ROS↑, 21,   mt-ROS↑, 1,   TrxR↓, 4,   TrxR1?, 1,   TrxR1↓, 2,  

Metal & Cofactor Biology ⓘ

FTH1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   Glycolysis↓, 1,   HK2↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 2,   Apoptosis↑, 3,   BAX↓, 1,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   cl‑Casp3∅, 1,   proCasp3↓, 1,   Casp7↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   JNK↑, 3,   MAPK↑, 1,   p38↑, 3,   PUMA↑, 1,   survivin↓, 2,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 2,  

Transcription & Epigenetics ⓘ

SETBP1↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   ER Stress↑, 4,   p‑PERK↑, 1,   XBP-1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↑, 1,   PARP↑, 1,   cl‑PARP↑, 3,   cl‑PARP∅, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 2,   P21↑, 2,   p‑RB1↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   ERK↑, 1,   GSK‐3β↓, 1,   mTOR↓, 3,   PTEN↑, 1,   RAS↓, 1,   STAT1↓, 1,   STAT3↓, 1,   STAT6↓, 1,   TumCG↓, 1,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 1,   FOSB↑, 1,   MMP9↓, 1,   SOX4↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 3,   TumMeta↓, 1,   Twist↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IKKα↓, 1,   IKKα↑, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 3,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 3,   BioEnh↑, 2,   ChemoSen↑, 2,   Dose↝, 2,   eff↓, 10,   eff↑, 14,   eff↝, 1,   Half-Life↝, 1,   MDR1↓, 1,   MRP1↓, 1,   RadioS↑, 1,   selectivity↑, 10,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,   toxicity↓, 1,   toxicity↑, 1,   TumW↓, 1,  
Total Targets: 119

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

GSH↑, 1,   GSSG∅, 1,   GSTA1↓, 1,   NQO1↑, 1,   NRF2↑, 1,   NRF2⇅, 1,   ROS↓, 1,   ROS↑, 1,   Trx↑, 1,   TrxR↑, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   eff↓, 1,   eff↑, 1,   Half-Life↑, 1,  

Functional Outcomes ⓘ

toxicity↓, 2,  
Total Targets: 18

Scientific Paper Hit Count for: eff, efficacy
25 Piperlongumine
1 Auranofin
1 Docetaxel
1 chitosan
1 Piperine
1 borneol
1 5-fluorouracil
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#:961  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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