Piperlongumine / FBPase 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)

FBPase, Fructose-1,6-Bisphosphatase: Click to Expand ⟱

Source:

Type:

Fructose-1,6-bisphosphatase (FBPase) is a key enzyme of gluconeogenesis that has garnered significant attention in cancer research. Altered metabolic pathways are hallmarks of cancer, and many tumors rely on aerobic glycolysis (the Warburg effect) rather than oxidative phosphorylation even in the presence of oxygen. In this context, the expression and activity of FBPase—primarily FBP1 and to some extent FBP2—play important roles in modulating cancer metabolism as well as impacting patient prognosis.

FBP1 (Fructose-1,6-Bisphosphatase 1) is a key enzyme in gluconeogenesis, the process by which cells generate glucose from non-carbohydrate sources. FBP1 is often downregulated in cancer cells, and its low expression is associated with poor prognosis.
FBP1 is a key enzyme in the regulation of the Warburg effect, a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. FBP1 activators are being developed as a potential therapeutic strategy for cancer treatment.

Key Role in Gluconeogenesis
-FBPase catalyzes the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate, which is a pivotal step in gluconeogenesis.
-This counteracts glycolysis—a pathway often upregulated in cancer cells to support rapid proliferation and biomass generation.

Altered FBPase Expression in Cancer
-A decrease or loss of FBP1 expression has been observed in several cancer types

FBP1:
-Primarily found in the liver and kidney.
-Plays a central role in gluconeogenesis by catalyzing the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
-Its expression is more frequently linked to altered metabolic states in various cancers (e.g., reduced FBP1 is often associated with a glycolytic and more aggressive tumor metabolism).

FBP2:
-Known as the muscle isoform of fructose-1,6-bisphosphatase.
-While it performs a similar catalytic function, its expression profile and regulation differ from FBP1 and it is less commonly associated with the metabolic rewiring observed in many cancers.

Scientific Papers found: Click to Expand⟱

992-

PL,

Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1

in-vivo,

BC,

zebrafish and nude mice

EPR↓, Glycolysis↓, GAPDH↓, GSTP1/GSTπ↝, FBPase↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

GSTP1/GSTπ↝, 1,

Core Metabolism/Glycolysis ⓘ

FBPase↑, 1, GAPDH↓, 1, Glycolysis↓, 1,

Angiogenesis & Vasculature ⓘ

EPR↓, 1,
Total Targets: 5

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: FBPase, Fructose-1,6-Bisphosphatase

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