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


PARP, poly ADP-ribose polymerase (PARP) cleavage: Click to Expand ⟱
Source:
Type:
Poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA.
PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors.
PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations.

PARP Family:
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death.
PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER).

PARP1 Overexpression:
In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported.
High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage).
Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.
Scientific Papers found: Click to Expand⟱
3138- VitC,    The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity
- in-vitro, RCC, RCC4 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-435 - in-vitro, Ovarian, SKOV3 - in-vitro, Colon, SW48 - in-vitro, GBM, U251
eff↑, Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines
Warburg↓,
BioAv↑, HIF increases the intracellular uptake of oxidized Vc through its transcriptional target glucose transporter 1 (GLUT1),
ROS↑, resulting high levels of intracellular Vc induce oxidative stress and massive DNA damage, which then causes metabolic exhaustion by depleting cellular ATP reserves.
DNAdam↑,
ATP↓,
eff↑, Activation of HIF increases the susceptibility to Vc-induced cell toxicity
necrosis↑, High intracellular levels of Vc increase ROS and trigger necrosis in VHL-defective renal cancer cells.
PARP↑, Activation of the PARP Pathway by Vc Depletes Intracellular ATP Reserves in VHL-defective Renal Cancer Cells

3133- VitC,    Vitamin C supplementation had no side effect in non-cancer, but had anticancer properties in ovarian cancer cells
- in-vitro, Ovarian, NA
*SVCT-2↑, In non-cancer cells, Vit C, at a pharmacological concentration, increased SVCT2 and decreased GLUT1, while the opposite effect was noted in cancer cells.
*GLUT1↓,
SVCT-2↓,
GLUT1↑,
TumCP↓, cancer cells, Vit C, in a pharmacological dose, decreased cell proliferation through an inhibitory effect on cyclin-dependent kinase 2 (CDK2) (4.4-fold; p < 0.01), mainly due to the stimulatory effect on the expression of CDK inhibitors, p21 and P53
CDK2↓,
PARP↓, At a pharmacological dose of 1 mM, Vit C decreased PARP expression (1.5-fold; p < 0.05).
selectivity↑, it's nontoxic effects on non-cancer cells

633- VitC,    Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment
- Analysis, NA, NA
Fenton↑,
ROS↑,
EMT↓, Ascorbic acid is also known to inhibit EMT of tumor cells
DNAdam↑,
PARP↑, DNA damage increases PARP activity, thereby decreasing NAD+ levels
NAD↓, NAD+
ATP↓,
Apoptosis↑,

632- VitC,    High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients
- Review, NA, NA
SVCT-2∅, vitamin C entry into cells is tightly regulated by SVCT
ROS↑, well-recognized pro-oxidant effects
Hif1a↓, HIF-1α proteasomal degradation
PARP∅, Moreover, vitamin C action at DNA levels may provide the rationale basis for combination therapies with PARP inhibitors and hypomethylating agents.
TET2↑, However, the ability of vitamin C to restore TET2 activity seems to depend on N- and C-terminal lysine acetylation and type of TET2 mutations

627- VitC,    High-Dose Vitamin C for Cancer Therapy
- Review, NA, NA
ROS↑,
PARP↑, ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+
GAPDH↓, Hindering GAPDH can result in an “energy crisis”, due to the decrease in ATP production
DNAdam↑,
ATP↓,


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

Results for Effect on Cancer/Diseased Cells:
Apoptosis↑,1,   ATP↓,3,   BioAv↑,1,   CDK2↓,1,   DNAdam↑,3,   eff↑,2,   EMT↓,1,   Fenton↑,1,   GAPDH↓,1,   GLUT1↑,1,   Hif1a↓,1,   NAD↓,1,   necrosis↑,1,   PARP↓,1,   PARP↑,3,   PARP∅,1,   ROS↑,4,   selectivity↑,1,   SVCT-2↓,1,   SVCT-2∅,1,   TET2↑,1,   TumCP↓,1,   Warburg↓,1,  
Total Targets: 23

Results for Effect on Normal Cells:
GLUT1↓,1,   SVCT-2↑,1,  
Total Targets: 2

Scientific Paper Hit Count for: PARP, poly ADP-ribose polymerase (PARP) cleavage
5 Vitamin C (Ascorbic Acid)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:166  Target#:239  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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