Lycopene / Keap1 Cancer Research Results

Lyco, Lycopene: Click to Expand ⟱
Features:
Lycopene is a naturally occurring carotenoid found predominantly in tomatoes and other red fruits and vegetables.

Antioxidant Properties:
-Lycopene is a powerful antioxidant. It helps neutralize free radicals, which can reduce oxidative stress—a factor implicated in cancer development. Possible concern about interfering with chemotherapy and radiation therapy. However this review disagrees.
Inflammation Reduction:
-Some studies suggest that lycopene may help lower levels of inflammation, another process linked to cancer progression

At supraphysiological or extremely high concentrations, lycopene may have the potential to switch from an antioxidant to a prooxidant role
-The prooxidant effect of lycopene has been observed under conditions of high oxygen tension. In vitro studies have suggested that in environments with elevated oxygen levels, lycopene might promote rather than neutralize the production of reactive oxygen species (ROS).
-The presence of metal ions (such as iron or copper) in the environment can catalyze reactions where antioxidants, including lycopene, contribute to oxidative processes. These metals can interact with lycopene, potentially leading to the formation of radicals.

The mevalonate pathway produces cholesterol and a variety of isoprenoids, which are important for maintaining cell membrane integrity, protein prenylation, and other essential cellular functions.
-One of the primary enzymes in this pathway is HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase), which is the target of statin drugs used for lowering cholesterol. Some studies suggest that lycopene might downregulate the activity of HMG-CoA reductase or other enzymes in the mevalonate pathway. By doing so, lycopene could potentially reduce the synthesis of cholesterol and isoprenoids that are necessary for rapid cell proliferation—an especially relevant aspect in cancer cells.

Lycopene typically used in a 100mg/day range for cancer (inhibition of the the Melavonate Pathway)
-also has antiplatelet aggregation capability.

-Note half-life 16–20 days.
BioAv Heat processing, especially when combined with a small amount of fat, significantly enhances lycopene’s bioaccessibility and absorption. (20% under optimal conditions)
Pathways:
- ROS usually goes down, but may go up or down depending on dose and environment. Lycopene may also be modified to be a "oxdiative product" which may change the behaviour.
- 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 : EMT↓, MMPs↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : EZH2↓, P53↑, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↓ ROS ↓ ROS Driver Potent antioxidant activity Lycopene is a strong singlet-oxygen quencher with antioxidant dominance
2 IGF-1 / PI3K → AKT signaling ↓ IGF-1 signaling; ↓ AKT ↔ minimal Secondary Growth factor signaling attenuation Reduced IGF-1–driven proliferation is a key cancer-relevant effect
3 Cell cycle regulation ↑ G0/G1 arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle effects reflect growth factor modulation
4 Gap junction communication (connexins) ↑ gap junction signaling ↑ gap junction signaling Secondary Normalization of cell–cell communication Enhanced gap junctions are associated with reduced tumor progression
5 NF-κB / inflammatory signaling ↓ inflammatory signaling ↓ inflammatory tone Secondary Anti-inflammatory environment Inflammation reduction contributes to chemopreventive effects


Keap1, Kelch-like ECH-associated protein 1: Click to Expand ⟱
Source:
Type:
Kelch-like ECH-associated protein 1 (Keap1) is a key regulator of the transcription factor Nrf2.

-In several tumor types, loss of Keap1 function (either due to gene mutations or low protein expression) results in unrestrained Nrf2 activity.
• Persistent Nrf2 activation is thought to:
 - Provide tumor cells with enhanced protection against oxidative stress.
 - Contribute to chemoresistance and radioresistance.
 - Promote metabolic reprogramming that fuels tumor growth.

• Thus, in many cancers, altered Keap1 status can serve as an indicator of poor prognosis and has been investigated as a potential target for therapeutic intervention.


Scientific Papers found: Click to Expand⟱
4800- Lyco,    Recent insights on pharmacological potential of lycopene and its nanoformulations: an emerging paradigm towards improvement of human health
- Review, Var, NA
*antiOx↑, Keap1↝, NF-kB↝, NRF2↝, PI3K↝, Akt↝, mTOR↝, *GutMicro↑,
1709- Lyco,    Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation
- in-vitro, Nor, JB6
*antiOx↑, *NRF2↑, *GSH/GSSG↓, *Catalase↝, *GR↝, *SOD↝, *GPx↝, *GSH↑, *Keap1↓, *p62↑,

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

Keap1↝, 1,   NRF2↝, 1,  

Cell Death

Akt↝, 1,  

Proliferation, Differentiation & Cell State

mTOR↝, 1,   PI3K↝, 1,  

Immune & Inflammatory Signaling

NF-kB↝, 1,  
Total Targets: 6

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 2,   Catalase↝, 1,   GPx↝, 1,   GSH↑, 1,   GSH/GSSG↓, 1,   Keap1↓, 1,   NRF2↑, 1,   SOD↝, 1,  

Autophagy & Lysosomes

p62↑, 1,  

Hormonal & Nuclear Receptors

GR↝, 1,  

Clinical Biomarkers

GutMicro↑, 1,  
Total Targets: 11

Scientific Paper Hit Count for: Keap1, Kelch-like ECH-associated protein 1
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#:119  Target#:1174  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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