condition found tbRes List
VitC, Vitamin C (Ascorbic Acid): Click to Expand ⟱
Features:
High-dose vitamin C: Some studies have suggested that high-dose vitamin C may be effective in treating certain types of cancer, such as ovarian cancer and pancreatic cancer.
Symptoms of vitamin C deficiency include fatigue, weakness, poor wound healing, ecchymoses, xerosis, lower extremity edema, and musculoskeletal pain—most of them are often observed in end-stage cancer patients. -Vitamin C is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function.
-Ascorbic Acid, Different levels in different Organs
Homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. -(Note the Oncomagnetic success in the brain also was then under conditions of high Vitamin C)

-Ascorbic acid is an electron donor
Ascorbic Acid, can be a Pro-oxidant
"The pro-oxidative activity of ascorbic acid (Figure 2) is associated with the interaction with transition metal ions (especially iron and copper). Under conditions of high, millimolar ascorbate concentration, vitamin C catalyzes the reduction of free transition metal ions, which causes the formation of oxygen radicals."
Ascorbic Acid, formation of H2O2 (Hydrogen Peroxide)
Many studies indicate the toxicity of ascorbate to cancer cells. Much evidence indicates that the underlying phenomenon is the pro-oxidative activity of ascorbate, which induces the formation of H2O2 and oxidative stress.
"ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2)"
-High dose VitC therapy may not be for those with kidney problems
-Oral supplement up to 10g/day?
-Direct regulator of TET↑
-caution for (G6PD-) deficient patients receiving vitamin C infusions

-Note plasma half-life 30mins to 1hr, 1.5-2hr elimination half-life.
oral BioAv water soluble, but has limitiations as 100mg yeilds 60uM/L in plasma, but 1000mg only yeilds 85uM/L. mM concentration are required for effectiveness on cancer cells. Hence why IV administration is common. Boosting HIF increases the intracellular uptake of oxidized VitC
Pathways:
- high dose induces ROS production in cancer cells. Otherwise well known antioxidant in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Caspases↑, DNA damage↑, cl-PARP↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓">NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, NF-κB↓,
- reactivate genes thereby inhibiting cancer cell growth : P53↑, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓,
- Others: PI3K↓, AKT↓, STAT↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective,

- Selectivity: Cancer Cells vs Normal Cells


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
3113- VitC,    Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
- in-vitro, Nor, NA
TET2↑, intravenous vitamin C treatment in mice abrogates cancer progression through direct TET2 function restoration in cancer cells
NF-kB↑, Vitamin C triggers extensive demethylation at NF-κB/p65 binding sites

3115- VitC,    The NF-κB Transcriptional Network Is a High-Dose Vitamin C-Targetable Vulnerability in Breast Cancer
- in-vitro, BC, NA
NF-kB↓, vitamin C can regulate the activation of NF-κB by inhibiting specific NF-κB-dependent genes and multiple stimuli.
Hif1a↓, Vitamin C activates enzymes that are able to inhibit NF-κB and HIF-1α as well as their target genes.
P53↑, vitamin C was reported to decrease NF-κB function and increase p53 overexpression and stability

3116- VitC,    Vitamin C Inhibits NF-kB Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase
- in-vitro, Nor, ECV304 - in-vitro, Nor, HUVECs
*NF-kB↓, vitamin C inhibited TNF-mediated NF-kB activation in a dose-dependent manner,
*p38↑, Vitamin C potently activates p38 MAPK
*MAPK↑,

3141- VitC,    High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer
- in-vitro, CRC, HCT116
Glycolysis↓, Vitamin C inhibits immune evasion by regulating glycolysis
eff↑, VitC suppresses tumor growth and enhances immunotherapy in combination with anti-PD-L1
PD-L1↓, We found that VitC inhibits aerobic glycolysis in HCT116 cells while also downregulating PD-L1 expression.
AMPK↑, VitC's activation of AMPK, which downregulates HK2 and NF-κB, ultimately resulting in reduced PD-L1 expression and increased T cell infiltration.
HK2↓,
NF-kB↓,
Warburg↓, Our research shows that high-dose VitC downregulating the Warburg effect, suppressing CRC growth
tumCV↓, After treatment with VitC, the cell viability of HCT116 cells significantly decreased
GLUT1↓, marked reduction in the mRNA level of glycolysis-related proteins GLUT1, PKM2, and LDHA
PKM2↓,
LDHA↓,
CD4+↑, Our research shows that high-dose VitC increases CD4+ and CD8+ T cell infiltration in tumor tissues by inhibiting PD-L1
CD8+↑,

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↑, vitamin K3- or vitamin C- induced apoptosis in leukemia cells by oxidative stress
H2O2↑, hydrogen peroxide generation,
NF-kB↑, activation of NF-κB,
P53↑, p53, c-Jun, protease caspase-3 activation
cJun↑,
Casp3↑,
MMP↓, mitochondria depolarization leading to nuclei fragmentation
DNAdam↑,
Dose?, Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM) or 100:1 (300 μM: 3 μM), respectively


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
AMPK↑,1,   Casp3↑,1,   CD4+↑,1,   CD8+↑,1,   cJun↑,1,   DNAdam↑,1,   Dose?,1,   eff↑,1,   GLUT1↓,1,   Glycolysis↓,1,   H2O2↑,1,   Hif1a↓,1,   HK2↓,1,   LDHA↓,1,   MMP↓,1,   NF-kB↓,2,   NF-kB↑,2,   P53↑,2,   PD-L1↓,1,   PKM2↓,1,   ROS↑,1,   TET2↑,1,   tumCV↓,1,   Warburg↓,1,  
Total Targets: 24

Results for Effect on Normal Cells:
MAPK↑,1,   NF-kB↓,1,   p38↑,1,  
Total Targets: 3

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
5 Vitamin C (Ascorbic Acid)
1 VitK3,menadione
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:166  Target#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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