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


ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
Scientific Papers found: Click to Expand⟱
2995- PL,    Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover
- in-vitro, Lung, H1975 - in-vitro, Lung, PC9 - in-vivo, NA, NA
Sp1/3/4↓, piperlongumine could enhance the interaction between E3 ligase RNF4 and Sp1, inhibit the phosphorylation of Sp1 at Thr739, facilitate the ubiquitination and degradation of Sp1, lead to c-Met destabilization, and trigger intrinsic apoptosis in resista
cMET↓,
Apoptosis↑,
Cyt‑c↑, piperlongumine promoted the release of cytochrome c from the mitochondria to the cytoplasm while facilitating the translocation of Bcl-2-associated X protein (Bax) to the mitochondria
p‑ERK↓, dose-dependent decrease in the protein levels of c-Met, phosphorylated ERK1/2 (p-ERK1/2), and p-Akt
p‑Akt↓,
TumCG↓, These data suggest that piperlongumine exhibits good tolerability and effectively inhibits tumor growth of osimertinib-resistant cells in vivo.

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↑, it is selectively toxic to cancer cells by generating reactive oxygen species (ROS)
selectivity↑,
tumCV↓, Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction.
TumCCA↑,
Apoptosis↑,
ERK↑, activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL
Akt↓,
mTOR↓,
neuroP↑, neuroprotective, and anticancer properties
Bcl-2↓, induces the downregulation of Bcl2 expression and the activation of caspase-3, poly (ADP-ribose) polymerase (PARP), and JNK
Casp3↑,
PARP↑,
JNK↑,
*toxicity↓, several whole-animal models, and it is highly safe when used in vivo
eff↓, Pre-treatment with N-acetylcysteine (NAC; a selective ROS scavenger) significantly reduced PL-mediated ROS activation
TumW↓, tumor weight in the PL (10 mg/kg) treatment group significantly decreased when compared with that in the control group

2948- PL,    The promising potential of piperlongumine as an emerging therapeutics for cancer
- Review, Var, NA
tumCV↓, inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases,
TumCP↓,
TumCI↓,
angioG↓,
EMT↓,
TumMeta↓,
*hepatoP↑, A study demonstrated the hepatoprotective effects of P. longum via decreasing the rate of lipid peroxidation and increasing glutathione (GSH) levels
*lipid-P↓,
*GSH↑,
cardioP↑, cardioprotective effect
CycB↓, downregulated the mRNA expression of the cell cycle regulatory genes such as cyclin B1, cyclin D1, cyclin-dependent kinases (CDK)-1, CDK4, CDK6, and proliferating cell nuclear antigen (PCNA)
cycD1↓,
CDK2↓,
CDK1↓,
CDK4↓,
CDK6↓,
PCNA↓,
Akt↓, suppression of the Akt/mTOR pathway by PL was also associated with the partial inhibition of glycolysis
mTOR↓,
Glycolysis↓,
NF-kB↓, Suppression of the NF-κB signaling pathway and its related genes by PL was reported in different cancers
IKKα↓, inactivation of the inhibitor of NF-κB kinase subunit beta (IKKβ)
JAK1↓, PL efficiently inhibited cell proliferation, invasion, and migration by blocking the JAK1,2/STAT3 signaling pathway
JAK2↓,
STAT3↓,
ERK↓, PL also negatively regulates ERK1/2 signaling pathways, thereby suppressing the level of c-Fos in CRC cells
cFos↓,
Slug↓, PL was found to downregulate slug and upregulate E-cadherin and inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells
E-cadherin↑,
TOP2↓, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8
P53↑,
P21↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
p‑HER2/EBBR2↓, ↓p-HER1, ↓p-HER2, ↓p-HER3
HO-1↑, ↑Apoptosis, ↑HO-1, ↑Nrf2
NRF2↑,
BIM↑, ↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt
p‑FOXO3↓,
NA↓,
Sp1/3/4↓, ↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET
cMyc↓,
EGFR↓,
survivin↓,
cMET↓,
NQO1↑, G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,
SOD2↑,
TrxR↓, G2/M cell cycle arrest, ↑apoptosis, ↑ROS, ↓GSH, ↓TrxR
MDM2↓, ↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis
p‑eIF2α↑,
ATF4↑,
CHOP↑,
MDA↑, ↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA
Ki-67↓, ↓Ki-67, ↓MMP-9, ↓Twist,
MMP9↓,
Twist↓,
SOX2↓, ↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug
Nanog↓,
OCT4↓,
N-cadherin↓,
Vim↓,
Snail↓,
TumW↓, ↓Tumor weight, ↓tumor growth
TumCG↓,
HK2↓, ↓HK2
RB1↓, ↓Rb
IL6↓, ↓IL-6, ↓IL-8,
IL8↓,
SOD1↑, ↑SOD1
RadioS↑, ombination with PL, very low intensity of radiation is found to be effective in cancer cells
ChemoSen↑, PL as a chemosensitizer which sensitized the cancer cells towards the commercially available chemotherapeutics
toxicity↓, PL does not have any adverse effect on the normal functioning of the liver and kidney.
Sp1/3/4↓, In vitro SKBR3 ↓Sp1, ↓Sp3, ↓Sp4
GSH↓, In vitro MCF-7 ↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα,
SOD↑, In vitro PANC-1, MIA PaCa-2 ↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   p‑Akt↓,1,   angioG↓,1,   Apoptosis↑,2,   ATF4↑,1,   BAX↑,1,   Bcl-2↓,2,   BIM↑,1,   cardioP↑,1,   Casp3↑,2,   Casp7↑,1,   Casp8↑,1,   CDK1↓,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   cFos↓,1,   ChemoSen↑,1,   CHOP↑,1,   cMET↓,2,   cMyc↓,1,   CycB↓,1,   cycD1↓,1,   Cyt‑c↑,1,   E-cadherin↑,1,   eff↓,1,   EGFR↓,1,   p‑eIF2α↑,1,   EMT↓,1,   ERK↓,1,   ERK↑,1,   p‑ERK↓,1,   p‑FOXO3↓,1,   Glycolysis↓,1,   GSH↓,1,   p‑HER2/EBBR2↓,1,   HK2↓,1,   HO-1↑,1,   IKKα↓,1,   IL6↓,1,   IL8↓,1,   JAK1↓,1,   JAK2↓,1,   JNK↑,1,   Ki-67↓,1,   MDA↑,1,   MDM2↓,1,   MMP9↓,1,   mTOR↓,2,   N-cadherin↓,1,   NA↓,1,   Nanog↓,1,   neuroP↑,1,   NF-kB↓,1,   NQO1↑,1,   NRF2↑,1,   OCT4↓,1,   P21↑,1,   P53↑,1,   PARP↑,1,   PCNA↓,1,   RadioS↑,1,   RB1↓,1,   ROS↑,1,   selectivity↑,1,   Slug↓,1,   Snail↓,1,   SOD↑,1,   SOD1↑,1,   SOD2↑,1,   SOX2↓,1,   Sp1/3/4↓,3,   STAT3↓,1,   survivin↓,1,   TOP2↓,1,   toxicity↓,1,   TrxR↓,1,   TumCCA↑,1,   TumCG↓,2,   TumCI↓,1,   TumCP↓,1,   tumCV↓,2,   TumMeta↓,1,   TumW↓,2,   Twist↓,1,   Vim↓,1,  
Total Targets: 86

Results for Effect on Normal Cells:
GSH↑,1,   hepatoP↑,1,   lipid-P↓,1,   toxicity↓,1,  
Total Targets: 4

Scientific Paper Hit Count for: ERK, ERK signaling
3 Piperlongumine
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:134  Target#:105  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page