Database Query Results : Vitamin C (Ascorbic Acid), , GRP78/BiP

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)
GRP78/BiP, HSPA5: Click to Expand ⟱
Source:
Type:
GRP78 (Pgp, BiP or ERp72) is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors.
-GRP78 protein, a marker for endoplasmic reticulum stress
-GRP78’s role as a master regulator of the unfolded protein response (UPR) and cellular stress responses
The association of P-gp and inhibition of cell death in cancerous cells has also been reported in several studies including in hepatocellular, colorectal, prostate cancer, and gastric cancer. Although counterintuitive due to its prominent role in cancer resistance, P-gp has been linked to favorable prognosis.
ERp72 can promote cancer cell proliferation, migration, and invasion by regulating various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways. Additionally, ERp72 can also inhibit apoptosis (programmed cell death) in cancer cells, which can contribute to tumor progression. Overexpressed in: Breast, lung colorectal, prostrate, ovarian, pancreatic.

-GRP78 is frequently upregulated in a variety of solid tumors and hematological malignancies.
-Overexpression of GRP78 in cancer cells is often regarded as a marker of increased ER stress due to the reduced oxygen and nutrient supply typically encountered in the tumor microenvironment.
-Elevated GRP78 levels can contribute to tumor cell survival by enhancing the adaptive UPR, allowing cancer cells to cope with therapeutic and metabolic stress.
Scientific Papers found: Click to Expand⟱
4561- SNP,  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↑, Nanosilver increased Nrf2 protein expression and disrupted the cell cycle at the G1 and G2/M phases.
TumCCA↑, AgNPs interact with DNA to stop the cell cycle and lead to apoptosis
ROS↑, Nanosilver induced significant mitochondrial oxidative stress in HCT116, whereas it did not in the non-cancer HIEC-6 and nanosilver/sodium ascorbate co-treatment was preferentially lethal to HCT116 cells,
selectivity↑,
*AntiViral↑, AgNPs are effective antiviral agents against various viruses such as human immunodeficiency virus, hepatitis B virus, and monkey pox virus through interaction with surface glycoproteins on the virus
*toxicity↝, Citrate and PVP-coated AgNPs have been found to be less toxic than non-coated AgNPs
ETC↓, AgNPs affects mitochondrial function through the disruption of the electron transport chain2,24,26,33,39–41
MMP↓, Studies have shown that exposure to AgNPs resulted in a decrease of mitochondrial membrane potential (MMP) in various in vitro and in vivo experiments
DNAdam↑, AgNPs has also been shown to interact with and induce damage to DNA, DNA strand breaks, DNA damage
Apoptosis↑, apoptosis induced by AgNPs were through membrane lipid peroxidation, ROS, and oxidative stress
lipid-P↑,
other↝, Several studies have showed AgNPs interact with various proteins such as haemoglobin, serum albumin, metallothioneins, copper transporters, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), and bacterial proteins.
UPR↑, Studies have shown exposure to AgNPs induces activation of the UPR
*GRP78/BiP↑, AgNPs induced increased levels of GRP78, phosphorylated PERK, phosphorylated eIF2-α, and phosphorylated IRE1α, spliced XBP1, cleaved ATF-6, CHOP, JNK and caspase 12
*p‑PERK↑,
*cl‑eIF2α↑,
*CHOP↑,
*JNK↑,
Hif1a↓, One study showed AgNPs inhibits HIF-1 accumulation and suppresses expression of HIF-1 target genes in breast cancer cells (MCF-7) and also found the protein levels of HIF-1α and HIF-1β decreased
AntiCan↑, Many studies have shown that ascorbic acid, on its own, has anti-cancer effects
*toxicity↓, However, when the rats were treated with both ascorbic acid and AgNPs, a decrease in toxic effects was observed in non-cancer parotid glands in rats
eff↑, Studies have shown both AgNPs and ascorbic acid have greater effects and toxicity in cancer cells relative to non-cancer cells

3110- VitC,    Vitamin C Attenuates Oxidative Stress, Inflammation, and Apoptosis Induced by Acute Hypoxia through the Nrf2/Keap1 Signaling Pathway in Gibel Carp (Carassius gibelio)
- in-vivo, Nor, NA
*IL2↑, Moreover, the levels of the inflammatory cytokines (tnf-α, il-2, il-6, and il-12) were increased by enhancing the Nrf2/Keap1 signaling pathway
*IL6↑,
*IL12↑,
*NRF2↑,
*Catalase↑, Upregulation of the antioxidant enzymes activity (CAT, SOD, and GPx); T-AOC;
*SOD↑,
*GPx↑,
*GRP78/BiP↓, The expression of GRP78 protein in the liver and endoplasmic reticulum stress and apoptosis induced by hypoxia were inhibited by VC.
*ER Stress↓,

3149- VitC,    Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice through suppressing inflammatory reaction and ER stress
- in-vivo, Nor, NA
*hepatoP↑, Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice
*ALAT↓, showed in reductions of serological levels of transaminases (ALT and AST), lipids (TG and TC), fasting glucose and insulin, inflammatory cytokines (TNF-α and IL6)
*AST↓,
*TNF-α↓,
*IL6↓,
*ER Stress↓, Further, intrahepatic expressions of endoplasmic reticulum (ER) stress-based ATF6, eIF2α, GRP78, XBP1 proteins were down-regulated by treatments of VC.
*ATF6↓,
*eIF2α↓,
*GRP78/BiP↓,
*XBP-1↓,
*Inflam↓, suppressing hepatocellular inflammatory reaction and ER stress.

3147- VitC,    Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo−/− mice
- in-vivo, Nor, NA
*OS↑, life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo−/− mice.
*ER Stress↓,
*GRP78/BiP↓, There was a decrease in GRP78 in Gulo−/− mice treated with 0.4% ascorbate

3146- VitC,    Vitamin C protects against hypoxia, inflammation, and ER stress in primary human preadipocytes and adipocytes
- in-vivo, Nor, NA
*Obesity↓, These findings indicate that Vitamin C can reduce obesity-associated cellular stress and thus provide a rationale for future investigations.
*ER Stress↓, Vitamin C prevented the increase in hypoxia (Fig. 1A–B), significantly reduced the induction of ER stress
*Inflam↓, nd ameliorated the increased expression of inflammatory genes
Hif1a↓, Vitamin C treatment for 24 and 48 h significantly reducing induction of HIF1α protein by 30–40% and VEGFA and GLUT1 mRNA by 40–80%
VEGF↓,
GLUT1↓,
GRP78/BiP↓, significantly reversing the effects of TNFα+PA pre-treatment only on GRP78 induction, by 30–40%


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

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,1,   Apoptosis↑,1,   DNAdam↑,1,   eff↑,1,   ETC↓,1,   GLUT1↓,1,   GRP78/BiP↓,1,   Hif1a↓,2,   lipid-P↑,1,   MMP↓,1,   NRF2↑,1,   other↝,1,   ROS↑,1,   selectivity↑,1,   TumCCA↑,1,   UPR↑,1,   VEGF↓,1,  
Total Targets: 17

Results for Effect on Normal Cells:
ALAT↓,1,   AntiViral↑,1,   AST↓,1,   ATF6↓,1,   Catalase↑,1,   CHOP↑,1,   eIF2α↓,1,   cl‑eIF2α↑,1,   ER Stress↓,4,   GPx↑,1,   GRP78/BiP↓,3,   GRP78/BiP↑,1,   hepatoP↑,1,   IL12↑,1,   IL2↑,1,   IL6↓,1,   IL6↑,1,   Inflam↓,2,   JNK↑,1,   NRF2↑,1,   Obesity↓,1,   OS↑,1,   p‑PERK↑,1,   SOD↑,1,   TNF-α↓,1,   toxicity↓,1,   toxicity↝,1,   XBP-1↓,1,  
Total Targets: 28

Scientific Paper Hit Count for: GRP78/BiP, HSPA5
5 Vitamin C (Ascorbic Acid)
1 Silver-NanoParticles
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:166  Target#:356  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page