condition found tbRes List
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


TrxR, Thioredoxin Reductase: Click to Expand ⟱
Source:
Type:
TrxR is an enzyme that reduces Trx, allowing it to perform its reducing functions. It has been shown to have a role in cancer cell metabolism and survival.
TrxR is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer.

- Part of the thioredoxin system, which regulates reactive oxygen species (ROS).
- TrxR is a major antioxidant systems that maintains the intracellular redox homeostasis.
- Inhibition causes an increase in ROS.
- TrxR is often upregulated in cancer cells to help manage increased oxidative stress, it is seen as a potential therapeutic target. Inhibiting TrxR may result in increased ROS in cancer cells, pushing them toward apoptosis.
- TrxR is a selenoprotein—meaning it incorporates the trace element selenium in the form of the amino acid selenocysteine.

TrxR inhibitors:
-Piperlongumine
-Withania somnifera (Ashwagandha)
-Parthenolide
-EGCG
-Curcumin
-Myricetin
-Gambogic Acid
Scientific Papers found: Click to Expand⟱
1951- PL,    Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation
- in-vitro, Lung, A549
ROS↑, lipid-P↑, MMP↓, TumCCA↑, TrxR↓, eff↑,
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↓,
1949- PL,    Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor
- in-vitro, CRC, HCT116 - in-vitro, Cerv, HeLa
TrxR↓, selectivity↑, ROS↑, IDO1↓,
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↓,
1953- PL,    Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation
- in-vitro, Lung, A549 - in-vitro, Nor, WI38
ROS↑, selectivity↑, TrxR↓, TumCCA↑, GSH?, H2O2↑,
2649- PL,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
AntiCan↑, ROS↑, GSH↓, TrxR↓, Trx↓, Apoptosis↑, TumCCA↑, ER Stress↑, DNAdam↑, ChemoSen↑, BioAv↓,
2942- PL,    Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems
- in-vitro, CRC, CT26 - in-vitro, CRC, DLD1 - in-vivo, CRC, CT26
ROS↑, GSH↓, TrxR↓, RadioS↑, DNAdam↑, TumCCA↑, mitResp↓, GSTs↓, OS↑,
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↓, 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↓, cycD1↓, 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↓, NA↓, 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↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   p‑Akt↓,2,   angioG↓,2,   AntiCan↑,1,   AP-1↓,1,   Apoptosis↑,1,   ATF4↑,1,   ATF4↝,1,   BAX↑,1,   Bcl-2↓,1,   BIM↑,1,   BioAv↓,2,   BioAv↑,1,   BioEnh↑,1,   cardioP↑,1,   Casp3↑,2,   Casp7↑,2,   Casp8↑,1,   Casp9↑,1,   CDK1↓,1,   CDK2↓,1,   CDK4↓,2,   CDK6↓,2,   cFos↓,1,   ChemoSen↑,3,   CHOP↑,2,   cMET↓,1,   cMyc↓,2,   COX2↓,1,   CXCR4↓,1,   CycB↓,1,   cycD1↓,2,   Cyt‑c↑,1,   DNAdam↑,3,   E-cadherin↑,1,   eff↑,5,   EGFR↓,1,   p‑eIF2α↑,1,   EMT↓,1,   ER Stress↑,2,   ERK↓,1,   p‑FOXO3↓,1,   Glycolysis↓,2,   GSH?,1,   GSH↓,4,   GSK‐3β↓,1,   GSTs↓,1,   H2O2↑,1,   Half-Life↝,1,   p‑HER2/EBBR2↓,1,   HK2↓,2,   HO-1↑,2,   ICAM-1↓,1,   IDO1↓,1,   IKKα↓,1,   IL6↓,2,   IL8↓,1,   Inflam↓,1,   JAK1↓,1,   JAK2↓,1,   Ki-67↓,1,   lipid-P↑,1,   MDA↑,1,   MDM2↓,1,   MDR1↓,1,   mitResp↓,1,   MMP↓,2,   MMP9↓,2,   MRP1↓,1,   mTOR↓,3,   N-cadherin↓,1,   NA↓,1,   Nanog↓,1,   NF-kB↓,2,   NQO1↑,1,   NRF2↑,2,   OCT4↓,1,   OS↑,1,   P-gp↓,1,   P21↑,2,   p38↑,1,   P53↑,1,   cl‑PARP↑,1,   PCNA↓,1,   Prx4↑,1,   PTEN↑,1,   RadioS↑,3,   RAS↓,1,   RB1↓,1,   p‑RB1↓,1,   ROS↑,8,   selectivity↑,4,   Slug↓,1,   Snail↓,1,   SOD↑,1,   SOD1↑,1,   SOD2↑,1,   SOX2↓,1,   SOX4↑,1,   Sp1/3/4↓,3,   STAT1↓,1,   STAT3↓,2,   STAT6↓,1,   survivin↓,2,   TOP2↓,1,   toxicity↓,2,   Trx↓,1,   TrxR↓,9,   TumCCA↑,5,   TumCG↓,1,   TumCI↓,2,   TumCP↓,1,   tumCV↓,1,   TumMeta↓,2,   TumW↓,1,   Twist↓,2,   VEGF↓,1,   Vim↓,1,   XBP-1↑,1,   β-catenin/ZEB1↓,1,  
Total Targets: 120

Results for Effect on Normal Cells:
GSH↑,1,   hepatoP↑,1,   lipid-P↓,1,  
Total Targets: 3

Scientific Paper Hit Count for: TrxR, Thioredoxin Reductase
9 Piperlongumine
1 Piperine
1 5-fluorouracil
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:134  Target#:825  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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