Vitamin C (Ascorbic Acid) / CHOP Cancer Research Results

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
Selenium supplementation may protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress. Meaning it may decrease effectiveness of high dose VitC.(#4468)


CHOP, GADD153: Click to Expand ⟱
Source:
Type: Protein
GADD153 and CHOP (C/EBP-homologous protein) refer to the same protein. GADD153 stands for "Growth Arrest and DNA Damage-inducible protein 153," while CHOP stands for "C/EBP Homologous Protein."
DDIT3 (DNA Damage Inducible Transcript 3), also known as CHOP (C/EBP Homologous Protein), is a transcription factor that plays a significant role in the cellular response to stress, particularly in the context of the unfolded protein response (UPR) and apoptosis.

CHOP is an important component of the endoplasmic reticulum (ER) stress response. Research has shown that knockdown of CHOP not only enhances tunicamycin-induced autophagy, but also significantly attenuates ER stress-induced apoptosis in human colon cancer cells.
GADD153, also known as CHOP (C/EBP homologous protein), is a transcription factor that plays a significant role in cellular stress responses, particularly in the context of the endoplasmic reticulum (ER) stress response. It is part of the unfolded protein response (UPR), which is activated when there is an accumulation of misfolded proteins in the ER.


Scientific Papers found: Click to Expand⟱
4561- AgNPs,  VitC,    Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts
- in-vitro, CRC, HCT116 - in-vitro, Nor, HEK293
NRF2↑, TumCCA↑, ROS↑, selectivity↑, *AntiViral↑, *toxicity↝, ETC↓, MMP↓, DNAdam↑, Apoptosis↑, lipid-P↑, other↝, UPR↑, *GRP78/BiP↑, *p‑PERK↑, *cl‑eIF2α↑, *CHOP↑, *JNK↑, Hif1a↓, AntiCan↑, *toxicity↓, eff↑,
3107- VitC,    Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment
- Review, Var, NA
Risk↓, *ROS↓, ROS↑, VEGF↓, COX2↓, ER Stress↑, IRE1↑, JNK↑, CHOP↑, Hif1a↓, eff↑, Glycolysis↓, MMPs↓, TumMeta↓, YAP/TEAD↓, eff↑, TET1↑,

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

lipid-P↑, 1,   NRF2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics

ETC↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis

Glycolysis↓, 1,  

Cell Death

Apoptosis↑, 1,   JNK↑, 1,   YAP/TEAD↓, 1,  

Transcription & Epigenetics

other↝, 1,  

Protein Folding & ER Stress

CHOP↑, 1,   ER Stress↑, 1,   IRE1↑, 1,   UPR↑, 1,  

DNA Damage & Repair

DNAdam↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Migration

MMPs↓, 1,   TET1↑, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature

Hif1a↓, 2,   VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,  

Drug Metabolism & Resistance

eff↑, 3,   selectivity↑, 1,  

Functional Outcomes

AntiCan↑, 1,   Risk↓, 1,  
Total Targets: 26

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

ROS↓, 1,  

Cell Death

JNK↑, 1,  

Protein Folding & ER Stress

CHOP↑, 1,   cl‑eIF2α↑, 1,   GRP78/BiP↑, 1,   p‑PERK↑, 1,  

Functional Outcomes

toxicity↓, 1,   toxicity↝, 1,  

Infection & Microbiome

AntiViral↑, 1,  
Total Targets: 9

Scientific Paper Hit Count for: CHOP, GADD153
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#:166  Target#:490  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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