Lycopene / P21 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


P21, P21: Click to Expand ⟱
Source:
Type: Proapototic
cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21
Scientific Papers found: Click to Expand⟱
4792- Lyco,    A Comprehensive Review on the Molecular Mechanism of Lycopene in Cancer Therapy
- Review, Var, NA
*AntiCan↑, *antiOx↑, Inflam↓, Wnt↓, β-catenin/ZEB1↓, *ROS↓, BioAv↑, ROS↓, Risk↓, PGE2↓, COX2↓, p‑ERK↓, P21↑, MMP7↓, MMP9↓, ChemoSen↑, eff↑,
4791- Lyco,    Investigating into anti-cancer potential of lycopene: Molecular targets
- Review, Var, NA
*antiOx↑, TumCP↓, TumCCA↓, Apoptosis↑, TumCI↓, angioG↓, TumMeta↓, *Risk↓, cycD1/CCND1↓, CycD3↓, cycE/CCNE↓, CDK2↓, CDK4↓, Bcl-2↓, P21↑, p27↑, P53↑, BAX↑, selectivity↑, MMP↓, Cyt‑c↑, Wnt↓, eff↑, PPARγ↑, LDL↓, Akt↓, PI3K↓, mTOR↓, PDGF↓, NF-kB↓, eff↑,
1708- Lyco,    The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies
- Review, Var, NA
OS↑, ChemoSen↑, QoL↑, PSA∅, eff↑, AntiCan↑, AntiCan↑, angioG↓, VEGF↓, Hif1a↓, SOD↑, Catalase↑, GPx↑, GSH↑, GPx↑, GR↑, MDA↓, NRF2↑, HO-1↑, COX2↓, PGE2↓, NF-kB↓, IL4↑, IL10↑, IL6↓, TNF-α↓, PPARγ↑, TumCCA↑, FOXO3↓, Casp3↑, IGF-1↓, p27↑, STAT3↓, CDK2↓, CDK4↓, P21↑, PCNA↓, MMP7↓, MMP9↓,
3276- Lyco,    Lycopene modulates cellular proliferation, glycolysis and hepatic ultrastructure during hepatocellular carcinoma
- in-vivo, HCC, NA
G6PD↓, PCNA↓, cycD1/CCND1↓, P21↑, Hif1a↓, Glycolysis↓,
3277- Lyco,    Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent
- Review, Var, NA
antiOx↑, TumCP↓, Apoptosis↑, TumMeta↑, ChemoSen↑, BioAv↓, Dose↝, BioAv↓, BioAv↑, SOD↑, Catalase↑, GPx↑, IL2↑, IL4↑, IL1↑, TNF-α↑, GSH↑, GPx↑, GSTA1↑, GSR↑, PPARγ↑, Casp3↑, NF-kB↓, COX2↓, Bcl-2↑, BAX↓, P53↓, CHK1↓, Chk2↓, γH2AX↓, DNAdam↓, ROS↓, P21↑, PCNA↓, β-catenin/ZEB1↓, PGE2↓, ERK↓, cMyc↓, cycE/CCNE↓, JAK1↓, STAT3↓, SIRT1↑, cl‑PARP↑, cycD1/CCND1↓, TNF-α↓, IL6↓, p65↓, MMP2↓, MMP9↓, Wnt↓,
3275- Lyco,    Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer
- Review, Var, NA
TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, P21↑, P53↑, GSK‐3β↓, p27↓, Akt↓, mTOR↓, ROS↓, MMPs↓, TumCI↓, TumCMig↓, NF-kB↓, *iNOS↓, *COX2↓, lipid-P↓, GSH↑, NRF2↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 4,   GSH↑, 3,   GSR↑, 1,   GSTA1↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 3,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   G6PD↓, 1,   Glycolysis↓, 1,   LDL↓, 1,   PPARγ↑, 3,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-2↑, 1,   Casp3↑, 2,   Chk2↓, 1,   Cyt‑c↑, 1,   p27↓, 1,   p27↑, 2,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   DNAdam↓, 1,   P53↓, 1,   P53↑, 2,   cl‑PARP↑, 1,   PCNA↓, 3,   γH2AX↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycD1/CCND1↓, 4,   CycD3↓, 1,   cycE/CCNE↓, 3,   P21↑, 6,   TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   p‑ERK↓, 1,   FOXO3↓, 1,   GSK‐3β↓, 1,   IGF-1↓, 1,   mTOR↓, 2,   PI3K↓, 1,   STAT3↓, 2,   Wnt↓, 3,  

Migration ⓘ

MMP2↓, 1,   MMP7↓, 2,   MMP9↓, 3,   MMPs↓, 1,   PDGF↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   TumMeta↑, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   Hif1a↓, 2,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IL1↑, 1,   IL10↑, 1,   IL2↑, 1,   IL4↑, 2,   IL6↓, 2,   Inflam↓, 1,   JAK1↓, 1,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 3,   PSA∅, 1,   TNF-α↓, 2,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

GR↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   ChemoSen↑, 3,   Dose↝, 1,   eff↑, 4,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 2,   PSA∅, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   OS↑, 1,   QoL↑, 1,   Risk↓, 1,  
Total Targets: 95

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ROS↓, 1,  

Cell Death ⓘ

iNOS↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   Risk↓, 1,  
Total Targets: 6

Scientific Paper Hit Count for: P21, P21
6 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#:234  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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