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↓, 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


MMPs, Matrix metalloproteinases: Click to Expand ⟱
Source:
Type:
Family of zinc-dependent proteolytic enzymes that play a key role in degrading the extracellular matrix (ECM).; are metalloproteinases that are calcium-dependent zinc-containing endopeptidases;[1] other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.[2]
MMP secretion: matrix metalloproteinase (MMP) is a kind of enzymes secreted.
by tumor cell to degrade ECM, facilitating the migration of tumor cells.

MMPs are generally considered protumorigenic due to their role in promoting tumor invasion, metastasis, and angiogenesis. They facilitate the breakdown of the extracellular matrix, allowing cancer cells to invade surrounding tissues and spread to distant sites.
Scientific Papers found: Click to Expand⟱
3107- VitC,    Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment
- Review, Var, NA
Risk↓, VitC supplementation resulted in dose-dependent reductions in all-cause mortality and the risk of various cancers
*ROS↓, Vitamin C (VitC) at the physiological dose (μM) is known to exhibit antioxidant properties.
ROS↑, However, it functions as a prooxidant at the pharmacological dose (mM) achieved by intravenous administration.
VEGF↓, VitC suppressed tumor angiogenesis in colon cancer-bearing mice by downregulating the expression and secretion of VEGF-A and VEGF-D
COX2↓, VitC impairs COX-2 activity and inhibits VEGF mRNA expression in melanoma cells in a time-dependent manner
ER Stress↑, VitC increases the ER stress-mediated breast cancer apoptosis via activation of the IRE-JNK-CHOP signaling pathway, an effect independent of ROS
IRE1↑,
JNK↑,
CHOP↑,
Hif1a↓, On the one hand, VitC directly inhibits HIF-1α-mediated glycolysis-related genes expression and the downstream acidic metabolites
eff↑, ROS generated by VitC treatment exerts a synergistic effect with other glycolysis inhibitors, providing a combined therapeutic strategy
Glycolysis↓,
MMPs↓, VitC inhibits a variety of metalloproteinases (MMPs) mRNA, which degrade ECM and release growth factors that drive tumor metastasis
TumMeta↓,
YAP/TEAD↓, VitC treatment reduces YAP1 expression while upregulating SYNPO-2; therefore, inhibiting metastasis of TNBC
eff↑, VitC enhances the killing efficiency of Hep G2 cells by low-dose sorafenib in vitro.
TET1↑, VitC stimulation of TET2 activity in the renal cell carcinoma

3129- VitC,    Therapeutic treatment with vitamin C reduces focal cerebral ischemia-induced brain infarction in rats by attenuating disruptions of blood brain barrier and cerebral neuronal apoptosis
- in-vivo, Stroke, NA
*BBB↑, Vitamin C alone or combined with rt-PA significantly reduced blood brain barrier permeability, levels of MMP-9,
*MMP9↓,
*MMPs↓, Vitamin C attenuates disruptions of blood brain barrier, inhibits MMPs expressions, and protects tight junction proteins
*MMP2↓, Evan Blue dye extravasation and up-regulation of MMP2 and MMP9, both of which were attenuated by vitamin C treatment
*CLDN1↝, tight junction proteins Claudin-1,Claudin-5, and ZO-1, which helps to maintain the integration of BBB, were also protected by vitamin C treatment
*ZO-1↝,
eff↑, a supra-physiological dose of intravenous vitamin C, with its excellent safety profile and low cost, warrants further evaluation as an adjuvant agent with intravenous thrombolysis or endovascular thrombectomy in the early treatment of acute ischemic


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

Results for Effect on Cancer/Diseased Cells:
CHOP↑,1,   COX2↓,1,   eff↑,3,   ER Stress↑,1,   Glycolysis↓,1,   Hif1a↓,1,   IRE1↑,1,   JNK↑,1,   MMPs↓,1,   Risk↓,1,   ROS↑,1,   TET1↑,1,   TumMeta↓,1,   VEGF↓,1,   YAP/TEAD↓,1,  
Total Targets: 15

Results for Effect on Normal Cells:
BBB↑,1,   CLDN1↝,1,   MMP2↓,1,   MMP9↓,1,   MMPs↓,1,   ROS↓,1,   ZO-1↝,1,  
Total Targets: 7

Scientific Paper Hit Count for: MMPs, Matrix metalloproteinases
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:166  Target#:204  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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