Vitamin K2 / NRF2 Cancer Research Results

VitK2, Vitamin K2: Click to Expand ⟱
Features:
Vitamin K2 (menaquinone)
Menaquinone-4 (MK-4), a subtype of vitamin K2 Helps blood clot, calcium metabolise and heart health.
Bone health: Vitamin K2 helps to regulate calcium levels in the body, which can help to prevent conditions such as osteoporosis and fractures.
Vitamin K2 has been studied for its potential role in cancer prevention and treatment. Some of the key findings include:
-Shown to inhibit the growth of cancer cells, including those found in leukemia, lung cancer, and prostate cancer.
-Shown to induce apoptosis (cell death) in cancer cells, which can help to prevent the spread of cancer.
-Shown to have anti-angiogenic effects, which means it can help to prevent the formation of new blood vessels that feed cancer cells.
-Synergistic effects with other nutrients, such as vitamin D and calcium, to enhance its anti-cancer effects.

UBIAD1 is the enzyme that makes MK-4 inside tissues

Vitamin K2 exists in several forms known as menaquinones, with MK-4 and MK-7 being the most studied. MK-4 is often used in Japan for therapeutic purposes, whereas MK-7 (derived from bacterial fermentation) is widely available as a supplement in Western countries.
For bone and cardiovascular health—and by extension, exploring potential anticancer benefits—doses for MK-7 commonly range from 90 to 200 micrograms per day.


NRF2, nuclear factor erythroid 2-related factor 2: Click to Expand ⟱
Source: TCGA
Type: Antiapoptotic
Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response.
-One way to estimate Nrf2 induction is through the expression of NQO1.
NQO1, the most potent inducer:
SFN 0.2 μM,
quercetin (2.5 μM),
curcumin (2.7 μM),
Silymarin (3.6 μM),
tamoxifen (5.9 μM),
genistein (6.2 μM ),
beta-carotene (7.2μM),
lutein (17 μM),
resveratrol (21 μM),
indol-3-carbinol (50 μM),
chlorophyll (250 μM),
alpha-cryptoxanthin (1.8 mM),
and zeaxanthin (2.2 mM)

1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects.
2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death.
3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress

-In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies.
-Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate.
Decreased Nrf2 expression: Skine, Liver, Pancreatic.
-Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer
- "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1.

Nrf2 Inhibitors and Activators
Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin
Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api
- potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany

Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue.
– In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis.
– In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity.
– This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming.
– Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies.
– High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types.
– While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression.

NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS).
-Brusatol: most cited natural inhibitors of Nrf2.
-Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent.
-Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent .
-Oridonin:
-Wogonin: although its effects might be cell‑ and dose‑specific.
- Withaferin A

Scientific Papers found: Click to Expand⟱
2276- VitK2,    Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat
- in-vivo, Nor, NA
*Albumin↑, *AST↓, *ALAT↓, *Keap1↓, *NRF2↑, *HO-1↑, *COX2↓, *iNOS↓, *TNF-α↓, *TIMP1↓, *TGF-β↓, *ROS↓, *DNAdam↓, *Inflam↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

HO-1↑, 1,   Keap1↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis

ALAT↓, 1,  

Cell Death

iNOS↓, 1,  

DNA Damage & Repair

DNAdam↓, 1,  

Migration

TGF-β↓, 1,   TIMP1↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   Inflam↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers

ALAT↓, 1,   Albumin↑, 1,   AST↓, 1,  
Total Targets: 15

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
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#:168  Target#:226  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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