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


ChemoSen, chemo-sensitization: Click to Expand ⟱
Source:
Type:
The effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”.

Chemo-Sensitizers:
-Curcumin
-Resveratrol
-EGCG
-Quercetin
-Genistein
-Berberine
-Piperine: alkaloid from black pepper
-Ginsenosides: active components of ginseng
-Silymarin
-Allicin
-Lycopene
-Ellagic acid
-caffeic acid phenethyl ester
-flavopiridol
-oleandrin
-ursolic acid
-butein
-betulinic acid



Scientific Papers found: Click to Expand⟱
1846- dietFMD,  VitC,    A fasting-mimicking diet and vitamin C: turning anti-aging strategies against cancer
- Study, Var, NA
TumCG↓, FMDs delay tumor progression
ChemoSen↑, potentiate chemotherapy efficacy
ChemoSideEff↓, while protecting healthy tissues from chemo-associated side effects in different cancer models
ROS↑, presence of metals, and particularly iron, high dose of vitamin C exerts a pro-oxidant action by generating hydrogen peroxide and hydroxyl radicals via Fenton chemistry
Fenton↑,
H2O2↑,
eff↑, we show that FMD cycles potentiate high-dose vitamin C anti-cancer effects in a range of cancer types
HO-1↓, KRAS-mutant cancer cells respond to vitamin C treatment by up-regulating HO-1, and consequently limiting vitamin C pro-oxidant action. FMD is able to revert HO-1 up-regulation
DNAdam↑, increase in free reactive iron and oxygen species causing DNA damage and cell death
eff↑, we found that the nontoxic FMD + vitamin C combination therapy is as effective as oxaliplatin + vitamin C in delaying tumor progression while the triple FMD, vitamin C and chemotherapy combination treatment is the most effective.

1847- dietFMD,  VitC,    Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers
- in-vitro, PC, PANC1
TumCG↓, Fasting-mimicking diets delay tumor progression
ChemoSen↑, sensitize a wide range of tumors to chemotherapy
eff↑, vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1
HO-1↓, FMD reverses the effect of vitamin C on HO-1(downregulating HO-1)
Ferritin↓,
Iron↑, consequently increasing reactive iron, oxygen species, and cell death
ROS↑, Vitamin C’s pro-oxidant action is strictly dependent on metal-ion redox chemistry. In particular, free iron was shown to be a key player in vitamin C-induced cytotoxic effects
TumCD↑,
IGF-1↓, effects on the insulin-like growth factor 1 (IGF-1)
eff↓, When cancer cells were grown under STS conditions before and during treatment, vitamin C-mediated toxicity was strongly enhanced
eff↓, Conversely, KRAS-wild-type CRC (SW48, HT29), prostate cancer (PC-3), ovarian cancer (COV362) cell lines and a normal colon cell line (CCD841CoN) were resistant to vitamin C when used both as a single agent and in combination with STS

3120- VitC,    Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells
- in-vitro, lymphoma, NA
TET2↑, ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity
Smad1↑, AA treatment increased the expression of SMAD1, a tumor suppressor gene known to be suppressed by methylation, and increased chemosensitivity of lymphoma cells.
ChemoSen↑,
other↝, AA treatment produced a progressive decrease in DNA methylation and an increase in the hydroxymethylation fraction in a dose-dependent manner, correlating with the increase in TET activity

3148- VitC,    Antioxidants in brain tumors: current therapeutic significance and future prospects
- Review, Var, NA
*antiOx↑, At dietary concentrations, vitamin C exhibits an antioxidant mechanism and prevent tumorigenesis [74]. Vitamin C prevents DNA damage by reducing OS, thereby preventing carcinogenesis
*ROS↓,
chemoP↑, Vitamin C exhibits both chemopreventive and chemotherapeutic roles via antioxidant and prooxidant mechanisms, respectively
ChemoSen↑,
TET2↑, activating ten-eleven translocation proteins (TETs)
eff↑, A regular supplement of vitamin C during pregnancy was found to reduce the risk of the fetus in developing pediatric brain tumors
OS↑, ascorbate demonstrated safety and chemotherapeutic efficacy in prolonging life span and improving quality of life
QoL↑,
eff↑, Vitamin C has been found to enhance the chemotherapeutic effects of methotrexate on glioblastoma cells

3135- VitC,    The interplay between vitamin C and thyroid
- Review, Thyroid, NA
AntiCan↑, found anti‐cancer effects for intravenous (IV) administration of vitamin C
ChemoSen↑, vitamin C could enhance the efficacy of monotherapies agents like cisplatin, 23 gemcitabine, 44 , 45 , 46 sorafenib, 47 PLX4032 21 and 5‐fluorouracil 44 in different types of cancers
radioP↑, vitamins like vitamin E and vitamin C as antioxidant agents are game changers and can reduce the toxicity level of radiopharmaceuticals with a higher efficacy of vitamin C.
MAPK↓, Mechanistic studies have also revealed that vitamin C inhibits the MAPK/ERK and PI3K/AKT signalling pathways in BRAF wild‐type or mutant thyroid cancer cells.
ERK↓,
PI3K↓,
Akt↓,
QoL↑, Cancers can influence patients' quality of life, and vitamin C is shown to positively affect pain relief and well‐being.
OS↑, Altogether, high‐dose vitamin C was shown to prolong the survival duration of patients

1836- VitC,  VitK3,  Chemo,    Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib
- in-vitro, AML, NA
tumCV↓, Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%,
selectivity↑, but did not influence the viability of normal lymphocytes
Apoptosis↑, strong induction of apoptosis
eff↑, Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes.
ChemoSen↑, combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy.

2278- VitK2,  VitK3,  VitC,    Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect
- Review, Var, NA
ChemoSen↑, The analyzed data suggest that vitamin C&K can sensitize cancer cells to conventional chemotherapy, which allows achievement of a lower effective dose of the drug and minimizing the harmful side-effects.
ROS↑, modulation of redox-balance and induction of oxidative stress in cancer cells due to quinone structure of vitamin K.
eff↑, Vitamin C plus K3: A powerful redox-system to sensitize cancer cells towards chemotherapeutics


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   AntiCan↑,1,   Apoptosis↑,1,   chemoP↑,1,   ChemoSen↑,7,   ChemoSideEff↓,1,   DNAdam↑,1,   eff↓,2,   eff↑,7,   ERK↓,1,   Fenton↑,1,   Ferritin↓,1,   H2O2↑,1,   HO-1↓,2,   IGF-1↓,1,   Iron↑,1,   MAPK↓,1,   OS↑,2,   other↝,1,   PI3K↓,1,   QoL↑,2,   radioP↑,1,   ROS↑,3,   selectivity↑,1,   Smad1↑,1,   TET2↑,2,   TumCD↑,1,   TumCG↓,2,   tumCV↓,1,  
Total Targets: 29

Results for Effect on Normal Cells:
antiOx↑,1,   ROS↓,1,  
Total Targets: 2

Scientific Paper Hit Count for: ChemoSen, chemo-sensitization
7 Vitamin C (Ascorbic Acid)
2 diet FMD Fasting Mimicking Diet
2 VitK3,menadione
1 Chemotherapy
1 Vitamin K2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:166  Target#:1106  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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