Plumbagin / CDC25 Cancer Research Results

PLB, Plumbagin: Click to Expand ⟱
Features:
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naturally occurring naphthoquinone derivative.

–Plumbagin can undergo redox cycling to generate reactive oxygen species (ROS)
-apototosis, activation of caspases, modulation of Bax, Bcl‑2, loss of MMP.
-Cell cycle arrest in cancer cells, often at the G0/G1, or G2/M phases.
-May inhibit NF‑κB activation
– MAPK Pathways
– PI3K/Akt Pathway
-Downregulation of (VEGF) and matrix metalloproteinases (MMPs).

-Seems capable of raising ROS in normal and cancer cells (#2004)

-ic50 cancer cells 1-10uM, normal cells >10uM

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Oxidative stress (redox cycling) ↑ ROS Upstream cytotoxic trigger Plumbagin induces ROS; ROS generation is causally linked to cell death in cancer models (ref)
2 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Mitochondrial dysfunction Loss of mitochondrial membrane potential occurs during plumbagin-induced apoptotic progression (ref)
3 Intrinsic apoptosis (caspase cascade) ↑ caspase-dependent apoptosis Programmed cell death Plumbagin triggers apoptosis in leukemia and solid tumor cells; antioxidant rescue attenuates killing (ref)
4 NF-κB signaling ↓ NF-κB activation Reduced pro-survival / inflammatory transcription Demonstrates plumbagin suppresses NF-κB signaling in tumor/immune contexts (direction explicitly shown) (ref)
5 STAT3 signaling ↓ STAT3 phosphorylation Reduced survival & proliferation signaling Plumbagin suppresses constitutive and inducible STAT3 phosphorylation in cancer cells (ref)
6 PI3K–AKT–mTOR signaling ↓ PI3K/AKT/mTOR activity Survival pathway suppression Plumbagin inhibits PI3K/AKT/mTOR signaling in cancer cells with linked apoptosis/autophagy outcomes (ref)
7 Autophagy program ↑ autophagy Stress response (context-dependent role) Plumbagin induces autophagy alongside apoptosis; pathway involvement (p38, PI3K/AKT/mTOR) is demonstrated (ref)
8 Stress MAPK (p38 MAPK) ↑ p38 activation Stress signaling amplification p38 MAPK activation is implicated in plumbagin-driven apoptosis/autophagy signaling in cancer cells (ref)
9 Cell cycle control ↑ G2/M (or S–G2/M) arrest Proliferation blockade Plumbagin induces checkpoint arrest with changes in cyclins/CDKs consistent with growth inhibition (ref)
10 Death receptor axis (TRAIL receptors DR4/DR5) ↑ DR4/DR5 expression Sensitizes to TRAIL-mediated killing Plumbagin increases DR4/DR5 and enhances TRAIL killing; NAC blocks both ROS and receptor upregulation (ref)
11 EMT / invasion programs ↓ EMT (anti-invasive) Reduced metastasis-related phenotype Plumbagin suppresses epithelial–mesenchymal transition and stemness-related markers in cancer cells (ref)
12 Angiogenesis signaling (VEGFR2/VEGF-driven endothelial responses) ↓ angiogenesis signaling / function Anti-angiogenic effect Plumbagin inhibits tumor angiogenesis via interference with VEGFR2-mediated signaling in endothelial/tumor models (ref)


CDC25, Cell Division Cycle 25: Click to Expand ⟱
Source:
Type:
CDC25 (Cell Division Cycle 25) is a family of dual-specificity phosphatases that play a crucial role in regulating the cell cycle. There are three main isoforms of CDC25: CDC25A, CDC25B, and CDC25C. These proteins are involved in the activation of cyclin-dependent kinases (CDKs) by dephosphorylating them, which is essential for the progression of the cell cycle from G2 phase to mitosis.
CDC25 proteins, particularly CDC25A, are often found to be overexpressed in various types of cancer. This overexpression can lead to uncontrolled cell proliferation, as the normal regulatory mechanisms of the cell cycle are disrupted.
High levels of CDC25 have been associated with advanced stages of cancer and poor prognosis in several malignancies, including breast, colorectal, and prostate cancers.
CDC25 interacts with various oncogenes and tumor suppressor proteins, such as p53. The loss of p53 function, which is common in many cancers, can lead to increased CDC25 activity, further promoting tumorigenesis.
CDC25A overexpressed: breast, CRC, lung, prostate.
CDC25B: breast, ovarian, lung.
CDC25C: liver,breast, prostate.
Scientific Papers found: Click to Expand⟱
5162- PLB,    Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells
- vitro+vivo, Melanoma, A172
TumCG↓, TumCCA↑, Apoptosis↑, P21↑, CycB/CCNB1↓, cycA1/CCNA1↓, CDC2↓, CDC25↑, Bax:Bcl2↑, Casp9↑, ROS↑, JNK↑, ERK↑, eff↓,
5163- PLB,    Plumbagin suppresses epithelial to mesenchymal transition and stemness via inhibiting Nrf2-mediated signaling pathway in human tongue squamous cell carcinoma cells
- in-vitro, SCC, SCC25
TumCP↓, NRF2↓, TumCCA↑, EMT↓, CSCs↓, eff↓, ROS↑, CycB/CCNB1↓, CDK1↓, CDK2↓, CDC25↓, Vim↓, OCT4↓, SOX2↓, Nanog↓, BMI1↓, NQO1↓, GSTA1↓, HSP90↓, toxicity↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSTA1↓, 1,   NQO1↓, 1,   NRF2↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   CDC25↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Bax:Bcl2↑, 1,   Casp9↑, 1,   JNK↑, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 2,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   Nanog↓, 1,   OCT4↓, 1,   SOX2↓, 1,   TumCG↓, 1,  

Migration ⓘ

TumCP↓, 1,   Vim↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 2,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 30

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CDC25, Cell Division Cycle 25
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#:299  Target#:526  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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