Piperlongumine / Apoptosis 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)

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⟱

2970-

PL,

Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways

in-vitro,

AML,

AntiAg↑, TumCG↓, Apoptosis↑, PI3K↓, Akt↓, mTOR↓, p38↑, Casp3↑,

2995-

PL,

Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover

in-vitro,

Lung,

H1975

in-vitro,

Lung,

PC9

in-vivo,

NA,

Sp1/3/4↓, cMET↓, Apoptosis↑, Cyt‑c↑, p‑ERK↓, p‑Akt↓, TumCG↓,

1938-

PL,

Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation

Study,

PSA,

in-vivo,

NA,

Mice: 10 (PL = PPL low dose) and 30 (PH = PPL high dose) mg/kg dose of PPL was fixed for topical intervention

ROS↑, Apoptosis↑, MMP↓, TumCCA↑, DNAdam↑, STAT3↓, Akt↓, PCNA↓, Ki-67↓, cycD1/CCND1↓, Bcl-2↓, K17↓, HDAC↓, ROS↑, *IL1β↓, *IL6↓, *TNF-α↓, *IL17↓, *IL22↓,

1945-

PL,

SANG,

The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer

in-vitro,

Lung,

A549

1-8uM(PL), 0-2uM(SAN)

ic50, 8.03µM for PL and 2.19 µM for SAN

toxicity∅, Apoptosis↑, TumMeta↓, ROS↑, TumCCA↑,

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,

selectivity↑, ROS↑, BioAv↓, BioAv↑, Apoptosis↑, TumCCA↑, eff↑,

2649-

PL,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

AntiCan↑, ROS↑, GSH↓, TrxR↓, Trx↓, Apoptosis↑, TumCCA↑, ER Stress↑, DNAdam↑, ChemoSen↑, BioAv↓,

2940-

PL,

Piperlongumine Induces Reactive Oxygen Species (ROS)-dependent Downregulation of Specificity Protein Transcription Factors

in-vitro,

PC,

PANC1

 5-15 μM

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↓,

2941-

PL,

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

in-vivo,

BC,

MDA-MB-231

mice

in-vitro,

OS,

U2OS

in-vitro,

BC,

MDA-MB-453

ROS↑, Apoptosis↑, selectivity↑, *ROS∅, GSH↓, GSSG↑, H2O2↑, NO↑, Half-Life?,

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

 2 and 3 μM

in-vitro,

Thyroid,

8505C

in-vivo,

NA,

10 mg/kg

Nude mice

ROS↑, selectivity↑, tumCV↓, TumCCA↑, Apoptosis↑, ERK↑, Akt↓, mTOR↓, neuroP↑, Bcl-2↓, Casp3↑, PARP↑, JNK↑, *toxicity↓, eff↓, TumW↓,

2947-

PL,

Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer

Review,

Var,

TumCP↓, Apoptosis↑, TumCCA↑, ROS↑,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

ROS∅, 1,

Immune & Inflammatory Signaling ⓘ

IL17↓, 1, IL1β↓, 1, IL22↓, 1, IL6↓, 1, TNF-α↓, 1,

Clinical Biomarkers ⓘ

IL6↓, 1,

Functional Outcomes ⓘ

toxicity↓, 1,
Total Targets: 8

Scientific Paper Hit Count for: Apoptosis, Apoptosis

10 Piperlongumine
1 Sanguinarine
1 borneol

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#:14  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Piperlongumine / Apoptosis Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Immune & Inflammatory Signaling ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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