Lycopene / NO 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


NO, Nitric Oxide: Click to Expand ⟱
Source:
Type:
Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment.
Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS).

– In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer.

• Expression Patterns in Tumors:
– Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment.

– Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.


Scientific Papers found: Click to Expand⟱
3528- Lyco,    The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene
- Review, Nor, NA - Review, AD, NA - Review, Park, NA
*antiOx↑, *ROS↓, *BioAv↝, *Half-Life↑, *BioAv↓, *BioAv↑, *cardioP↑, *neuroP↑, *H2O2↓, *VitC↑, *VitE↑, *GPx↑, *GSH↑, *MPO↓, *GSTs↓, *SOD↑, *NF-kB↓, *IL1β↓, *IL6↓, *IL10↑, *MAPK↓, *Akt↓, *COX2↓, *TNF-α↓, *TGF-β1↑, *NO↓, *GSR↑, *NRF2↑, *HO-1↑, *TAC↑, *Inflam↓, *BBB↑, *neuroP↑, *memory↑,
3261- Lyco,    Lycopene and Vascular Health
- Review, Stroke, NA
*Inflam↓, *antiOx↑, *AntiAg↑, *cardioP↑, *SOD↑, *Catalase↑, *ROS↓, *mtDam↓, *cardioP↑, *NF-kB↓, *NO↓, *COX2↓, *LDL↓, *eff↑, *ER Stress↓, *BioAv↑, *eff↑, *MMPs↓, *COX2↓, *RAGE↓,
3278- Lyco,    Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells
- in-vitro, Colon, SW480
TNF-α↓, IL1β↓, IL6↓, iNOS↓, COX2↓, PGE2↓, NO↓, NF-kB↓, JNK↓, Inflam↓, MPO↓,
3264- Lyco,    Pharmacological potentials of lycopene against aging and aging‐related disorders: A review
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*antiOx↑, *ROS↓, *SOD↑, *Catalase↑, *GSH↑, *GSTs↑, *MDA↓, *lipid-P↓, *NRF2↑, *HO-1↑, *iNOS↓, *NO↓, *TAC↑, *NOX4↓, *Inflam↓, *IL1↓, *IL6↓, *IL8↓, *IL1β↓, *TNF-α↓, *TLR2↓, *TLR4↓, *VCAM-1↓, *ICAM-1↓, *STAT3↓, *NF-kB↓, *ERK↓, *BP↓, ROS↓, PGE2↓, cardioP↑, *neuroP↑, *creat↓, *RenoP↑, *CRM↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

MPO↓, 1,   ROS↓, 1,  

Cell Death

iNOS↓, 1,   JNK↓, 1,  

Angiogenesis & Vasculature

NO↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   PGE2↓, 2,   TNF-α↓, 1,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

cardioP↑, 1,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 3,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 2,   GSR↑, 1,   GSTs↓, 1,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   MDA↓, 1,   MPO↓, 1,   NOX4↓, 1,   NRF2↑, 2,   ROS↓, 3,   SOD↑, 3,   TAC↑, 2,   VitC↑, 1,   VitE↑, 1,  

Mitochondria & Bioenergetics

mtDam↓, 1,  

Core Metabolism/Glycolysis

CRM↑, 1,   LDL↓, 1,  

Cell Death

Akt↓, 1,   iNOS↓, 1,   MAPK↓, 1,  

Protein Folding & ER Stress

ER Stress↓, 1,  

Proliferation, Differentiation & Cell State

ERK↓, 1,   STAT3↓, 1,  

Migration

AntiAg↑, 1,   MMPs↓, 1,   RAGE↓, 1,   TGF-β1↑, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature

NO↓, 3,  

Barriers & Transport

BBB↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 3,   ICAM-1↓, 1,   IL1↓, 1,   IL10↑, 1,   IL1β↓, 2,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 3,   NF-kB↓, 3,   TLR2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   eff↑, 2,   Half-Life↑, 1,  

Clinical Biomarkers

BP↓, 1,   creat↓, 1,   IL6↓, 2,   RAGE↓, 1,  

Functional Outcomes

cardioP↑, 3,   memory↑, 1,   neuroP↑, 3,   RenoP↑, 1,  
Total Targets: 60

Scientific Paper Hit Count for: NO, Nitric Oxide
4 Lycopene
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#:563  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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