Lycopene / Casp3 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


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.


Scientific Papers found: Click to Expand⟱
4782- Lyco,    New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene
- Review, Var, NA
AntiCan↑, TumCP↓, TumCMig↓, TumCI↓, TumCA↓, ROS↓, MMP2↓, MMP7↓, MMP9↓, VEGF↓, E-cadherin↑, TIMP1↑, TIMP2↑, BioAv↝, *IL12↓, *TNF-α↓, *IL1↓, *IL1β↓, *IL6↓, COX2↓, iNOS↓, *radioP↑, NF-kB↓, survivin↓, Casp3↑, Bax:Bcl2↑,
4779- Lyco,    Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells
- in-vitro, PC, PANC1
ROS↓, NF-kB↓, tumCV↓, Casp3↑, Apoptosis↑, OCR↓, MMP↓, CIP2A↓, survivin↓, Casp3↑, Bax:Bcl2↑,
4777- Lyco,    Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells
- in-vitro, GC, AGS
*antiOx↑, tumCV↓, DNAdam↑, Apoptosis↑, cl‑Casp3↑, cl‑Casp9↑, Bax:Bcl2↑, ROS↓, NF-kB↓, COX2↓, EGFR↓, p38↓,
3531- Lyco,    Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system
- in-vivo, Nor, NA
*NRF2↑, *HO-1↑, *NQO1↑, *ROS↓, *mtDam↓, *Bcl-2↑, *BAX↓, *Casp9↓, *Casp3↓, *Apoptosis↓, *RenoP↑, *lipid-P↓, *SOD↑, *GPx↑, *Inflam↓, *TNF-α↓, *IL6↓, *IL10↓,
1715- Lyco,    Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence
- Review, Var, NA
antiOx↑, ROS↑, ChemoSen↑, selectivity↑, eff↓, Casp3↑, Casp7↑, Casp9↑, P53↑, BAX↑, DNAdam↑, mtDam↑, 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↓,
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↓,
3263- Lyco,    Lycopene protects against myocardial ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening
- in-vitro, Nor, H9c2 - in-vitro, Stroke, NA
*Apoptosis↓, *MMP↑, *Cyt‑c↓, *APAF1↓, *cl‑Casp9↓, *cl‑Casp3↓, *Bcl-2↑, *BAX↓, cardioP↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

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

Mitochondria & Bioenergetics

MMP↓, 1,   mtDam↑, 1,   OCR↓, 1,  

Core Metabolism/Glycolysis

cMyc↓, 1,   PPARγ↑, 2,   SIRT1↑, 1,  

Cell Death

Apoptosis↑, 3,   BAX↓, 1,   BAX↑, 1,   Bax:Bcl2↑, 3,   Bcl-2↑, 1,   Casp3↑, 6,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   Chk2↓, 1,   iNOS↓, 1,   p27↑, 1,   p38↓, 1,   survivin↓, 2,  

Transcription & Epigenetics

tumCV↓, 2,  

DNA Damage & Repair

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

Cell Cycle & Senescence

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

CIP2A↓, 1,   ERK↓, 1,   FOXO3↓, 1,   IGF-1↓, 1,   STAT3↓, 2,   Wnt↓, 1,  

Migration

E-cadherin↑, 1,   MMP2↓, 2,   MMP7↓, 2,   MMP9↓, 3,   TIMP1↑, 1,   TIMP2↑, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

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

Immune & Inflammatory Signaling

COX2↓, 4,   IL1↑, 1,   IL10↑, 1,   IL2↑, 1,   IL4↑, 2,   IL6↓, 2,   JAK1↓, 1,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 2,   PSA∅, 1,   TNF-α↓, 2,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors

GR↑, 1,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

EGFR↓, 1,   IL6↓, 2,   PSA∅, 1,  

Functional Outcomes

AntiCan↑, 3,   cardioP↑, 1,   OS↑, 1,   QoL↑, 1,  
Total Targets: 99

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   GPx↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics

MMP↑, 1,   mtDam↓, 1,  

Cell Death

APAF1↓, 1,   Apoptosis↓, 2,   BAX↓, 2,   Bcl-2↑, 2,   Casp3↓, 1,   cl‑Casp3↓, 1,   Casp9↓, 1,   cl‑Casp9↓, 1,   Cyt‑c↓, 1,  

Immune & Inflammatory Signaling

IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 1,   TNF-α↓, 2,  

Clinical Biomarkers

IL6↓, 2,  

Functional Outcomes

radioP↑, 1,   RenoP↑, 1,  
Total Targets: 29

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
8 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#:42  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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