VitK3,menadione / Casp3 Cancer Research Results

VitK3, VitK3,menadione: Click to Expand ⟱
Features:
Menadione (2-methyl-1,4-naphthoquinone, also termed vitamin K3)
Menadione-induced ROS generation is concentration-dependent and high concentrations trigger cell death.
Clinical trials conducted on patients with prostate cancer showed that ascorbic acid-menadione produced an immediate drop in tumor cell numbers through a mechanism named autoschizis.
Menadione (Vitamin K3) is a synthetic naphthoquinone compound. It is not used as a nutritional vitamin supplement in humans due to toxicity risk (particularly hemolysis and hepatotoxicity). Historically used in animal feed.
Mechanistically, menadione functions primarily as a redox-active quinone, capable of:
-Undergoing redox cycling
-Generating reactive oxygen species (ROS)
-Inducing oxidative stress
-Interacting with glutathione (GSH) systems
-Modulating mitochondrial function
It has been investigated in oncology research largely due to its pro-oxidant cytotoxic properties, not classical vitamin K–dependent clotting roles.

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 Redox cycling (quinone-mediated ROS generation) ROS ↑; oxidative stress ↑; apoptosis ↑ (dose-dependent) Oxidative injury risk ↑ (hemolysis, hepatotoxicity) P, R Primary cytotoxic mechanism Menadione undergoes one-electron redox cycling, generating superoxide and hydrogen peroxide; not selective for tumor cells.
2 Glutathione (GSH) depletion GSH ↓; redox buffering capacity ↓ Red cell vulnerability ↑ P, R Redox destabilization Conjugation and oxidative cycling consume GSH, amplifying oxidative stress.
3 Mitochondrial dysfunction ΔΨm ↓; ATP ↓; apoptosis signaling ↑ Energy stress in normal cells possible R, G Mitochondria-mediated apoptosis ROS and redox imbalance disrupt mitochondrial membrane potential.
4 DNA damage (oxidative) DNA strand breaks ↑ (reported) Genotoxic risk ↑ R, G Genome instability Often secondary to ROS accumulation rather than direct DNA intercalation.
5 Synergy with ascorbate (Vitamin C) Redox cycling ↑; cytotoxicity ↑ (reported in vitro) Systemic oxidative injury risk ↑ P, R Redox amplification Menadione can undergo redox cycling with ascorbate, increasing ROS production; largely preclinical data.
6 Topoisomerase interference (reported) Topo inhibition (context-dependent) R Secondary mechanism Some studies report interference with topoisomerase activity, but this is not the dominant mechanism.
7 Hemolysis risk (G6PD vulnerability) Red blood cell destruction risk ↑ R Major toxicity constraint Menadione can cause hemolytic anemia, especially in G6PD deficiency.
8 Hepatotoxicity Liver injury risk ↑ G Clinical toxicity constraint Historical reason for discontinuation as a human supplement.
9 Vitamin K–dependent clotting pathway Minimal physiologic role in humans Not equivalent to K1/K2 Classification clarification Menadione is a synthetic precursor; does not function identically to phylloquinone (K1) or menaquinones (K2).

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid redox cycling and ROS generation)
  • R: 30 min–3 hr (mitochondrial dysfunction, DNA damage signaling)
  • G: >3 hr (apoptosis, tissue-level toxicity outcomes)


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.


Scientific Papers found: Click to Expand⟱
5160- PLB,  VitK3,    Plumbagin, Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization
- in-vitro, Melanoma, U266
STAT3↓, cSrc↓, JAK1↓, JAK2↓, SHP1↑, cycD1/CCND1↓, Bcl-xL↓, VEGF↓, Casp3↑, cl‑PARP↑, TumCCA↑, ChemoSen↑,
1823- VitK2,  VitK3,    Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells
- in-vitro, CRC, NA - in-vivo, NA, NA
TumCP↓, TumCCA↑, Casp3↑,
1838- VitK3,  PDT,    Photodynamic Effects of Vitamin K3 on Cervical Carcinoma Cells Activating Mitochondrial Apoptosis Pathways
- in-vitro, Cerv, NA
eff↑, ROS↑, tumCV↓, TumCG↓, Apoptosis↑, cl‑Casp3↑, cl‑Casp9↑, Bcl-xL↑, Cyt‑c↑, Bcl-2↓,
1832- VitK3,  VitC,    Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism
- in-vitro, AML, K562
ROS↑, H2O2↑, NF-kB↑, P53↑, cJun↑, Casp3↑, MMP↓, DNAdam↑, Dose?,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

H2O2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics

MMP↓, 1,  

Cell Death

Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Bcl-xL↑, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,  

Kinase & Signal Transduction

cSrc↓, 1,  

Transcription & Epigenetics

cJun↑, 1,   tumCV↓, 1,  

DNA Damage & Repair

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

SHP1↑, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration

TumCP↓, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Immune & Inflammatory Signaling

JAK1↓, 1,   JAK2↓, 1,   NF-kB↑, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   Dose?, 1,   eff↑, 1,  
Total Targets: 30

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
4 VitK3,menadione
1 Plumbagin
1 Vitamin K2
1 Photodynamic Therapy
1 Vitamin C (Ascorbic Acid)
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#:230  Target#:42  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

Home Page