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


MMP2, metalloproteinase-2: Click to Expand ⟱
Source:
Type:
Matrix metalloproteinase-2 (MMP-2) is an enzyme that plays a significant role in the degradation of extracellular matrix components, which is crucial for various physiological processes, including tissue remodeling, wound healing, and angiogenesis.
Elevated levels of MMP-2 have been associated with poor prognosis in various cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
2973- PL,    The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, 4T1
MMP2↓, Piperlongumine-treated MDA-MB-231 cells showed reduced motility/invasiveness, decreased MMP2 and MMP9 expression,
MMP9↓,
IL6↓, increased miR-200c expression, reduced IL-6 synthesis, decreased expression of ZEB1 and Slug, increased E-cadherin expression, and epithelial-like morphology.
E-cadherin↑,
ROS↑, ROS accumulated in piperlongumine-treated cells,
EMT↓, Piperlongumine Suppresses EMT
Zeb1↓, EMT-promoting ZEB1 and Slug transcription factors was significantly downregulated
Slug↓,
TumMeta↓, sub-cytotoxic dose of piperlongumine prevented metastasis in a mouse model of TNBC
selectivity↑, capacity to induce apoptosis in cancer cells while sparing normal cells
NA↑, Low dose piperlongumine also suppressed the expression of MMP2 and MMP9,
GSH↓, The resulting depletion of ROS-scavenging GSH would be expected to cause oxidative stress due to the accumulation of intracellular ROS


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

Results for Effect on Cancer/Diseased Cells:
E-cadherin↑,1,   EMT↓,1,   GSH↓,1,   IL6↓,1,   MMP2↓,1,   MMP9↓,1,   NA↑,1,   ROS↑,1,   selectivity↑,1,   Slug↓,1,   TumMeta↓,1,   Zeb1↓,1,  
Total Targets: 12

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: MMP2, metalloproteinase-2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:134  Target#:201  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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