Database Query Results : Lycopene, , β-catenin/ZEB1

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


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
4793- Lyco,    Lycopene treatment inhibits activation of Jak1/Stat3 and Wnt/β-catenin signaling and attenuates hyperproliferation in gastric epithelial cells
- in-vitro, GC, AGS
antiOx↑, Lycopene is a potent antioxidant exhibiting anticancer effects.
AntiCan↑,
ROS↓, results show that lycopene reduced ROS levels and inhibited Jak1/Stat3 activation, alteration of Wnt/β-catenin multiprotein complex molecules, expression of c-Myc and cyclin E, and cell proliferation in H pylori–infected AGS cells.
JAK1↓,
STAT3↓,
Wnt↓,
β-catenin/ZEB1↓,
cMyc↓,
cycE↓,
TumCP↓,
Risk↓, Lycopene might be a potential and promising nutrient for preventing H pylori–associated gastric diseases including gastric cancer.

4792- Lyco,    A Comprehensive Review on the Molecular Mechanism of Lycopene in Cancer Therapy
- Review, Var, NA
*AntiCan↑, The antioxidant profile of lycopene promotes anticancerous properties that reduce cancer prevalence by activating cell signaling pathways and gene expression (involved in cancer cell proliferation).
*antiOx↑,
Inflam↓, Lycopene's anti-inflammatory properties suppresses the tumor growth and development- promoting pathways, such as the PI3K/Akt/mTOR pathway.
Wnt↓, anticancer property of lycopene is also evidenced by its inhibi- tory potential of the Wnt/β-catenin signaling pathway that is involved in cancer cell modulation and propagation.
β-catenin/ZEB1↓,
*ROS↓, Lycopene also suppresses and neutralizes oxidative stress and reactive oxygen species (ROS)-induced DNA damage, preventing gene mutation.
BioAv↑, high-pressure homogenization having 80 MPa pressure and 25°C temperature (Carpentieri et al. 2023),and freeze-dried tomatoes (Tan et al. 2021) have improved the bioavailability and bioaccessibility of lycopene.
ROS↓, ycopene against pancreatic acinar cells was determined, it was found that IL- 6 and NF-kB are suppressed by lycopene (2 or 5 μmol/L) after 2 h of cerulein activation, demonstrating their role in neutralizing ROS
Risk↓, Mia et al. (2023) determined prostate cancer-lowering properties of lycopene among 47,365 individuals.
PGE2↓, Lycopene also exhibited its suppressive effect by reducing PGE2, COX-2, and phosphorylated ERK1/2 protein (Marino et al. 2023).
COX2↓,
p‑ERK↓,
P21↑, lycopene and fish oil supplementation was revealed by the elevated expression of cell cycle inhibitors (p21 CIP1/WAF1 and p27Kip1) as well as by the reduced expression of MMP-7, MMP-9, COX-2, PGE2
MMP7↓,
MMP9↓,
ChemoSen↑, It was observed that lycopene and cisplatin act synergistically to arrest cell growth by enhancing Bax & Nrf2 expression and inactivating Bcl-2 and NF-kB pathways
eff↑, lycopene silver nanoparticles (LyAgNP) suppressed the progression of HeLa cells and COLO320DM cells

1013- Lyco,    Lycopene induces apoptosis by inhibiting nuclear translocation of β-catenin in gastric cancer cells
- in-vitro, GC, AGS
Apoptosis↑,
DNAdam↑,
Bax:Bcl2↑,
ROS↓, AGS cells. The results showed that lycopene reduces the levels of ROS
β-catenin/ZEB1↓,
p‑GSK‐3β↓,
APC↑,
β-TRCP↑,
cMyc↓,
cycD1↓,

3277- Lyco,    Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent
- Review, Var, NA
antiOx↑, lycopene provides a strong antioxidant activity that is 100 times more effective than α-tocopherol and more than double effective that of β-carotene
TumCP↓, In vivo and in vitro experiments have demonstrated that lycopene at near physiological levels (0.5−2 μM) could inhibit cancer cell proliferation [[22], [23], [24]], induce apoptosis [[25], [26], [27]], and suppress metastasis [
Apoptosis↑,
TumMeta↑,
ChemoSen↑, lycopene can increase the effect of anti-cancer drugs (including adriamycin, cisplatin, docetaxel and paclitaxel) on cancer cell growth and reduce tumour size
BioAv↓, low water solubility and bioavailability of lycopene
Dose↝, The concentration of lycopene in plasma (daily intake of 10 mg lycopene) is approximately 0.52−0.6 μM
BioAv↓, significant decrease in lycopene bioavailability in the elderly
BioAv↑, oils and fats favours the bioavailability of lycopene [80], while large molecules such as pectin can hinder the absorption of lycopene in the small intestine due to their action on lipids and bile salt molecules
SOD↑, GC: 50−150 mg/kg BW/day ↑SOD, CAT, GPx ↑IL-2, IL-4, IL-10, TNF-α ↑IgA, IgG, IgM ↓IL-6
Catalase↑,
GPx↑,
IL2↑, lycopene treatment significantly enhanced blood IL-2, IL-4, IL-10, TNF-α levels and reduced IL-6 level in a dose-dependent manner.
IL4↑,
IL1↑,
TNF-α↑,
GSH↑, GC: ↑GSH, GPx, GST, GR
GPx↑,
GSTA1↑,
GSR↑,
PPARγ↑, ↑GPx, SOD, MDA ↑PPARγ, caspase-3 ↓NF-κB, COX-2
Casp3↑,
NF-kB↓,
COX2↓,
Bcl-2↑, AGS cells Lycopene 5 μM ↑Bcl-2 ↓Bax, Bax/Bcl-2, p53 ↓Chk1, Chk2, γ-H2AX, DNA damage ↓ROS Phase arrest
BAX↓,
P53↓,
CHK1↓,
Chk2↓,
γH2AX↓,
DNAdam↓,
ROS↓,
P21↑, CRC: ↑p21 ↓PCNA, β-catenin ↓COX-2, PGE2, ERK1/2 phosphorylated
PCNA↓,
β-catenin/ZEB1↓,
PGE2↓,
ERK↓,
cMyc↓, AGS cells: ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS
cycE↓,
JAK1↓,
STAT3↓,
SIRT1↑, Huh7: ↑SIRT1 ↓Cells growth ↑PARP cleavage ↓Cyclin D1, TNFα, IL-6, NF-κB, p65, STAT3, Akt activation ↓Tumour multiplicity, volume
cl‑PARP↑,
cycD1↓,
TNF-α↓,
IL6↓,
p65↓,
MMP2↓, SK-Hep1 human hepatoma cells Lycopene 5, 10 μM ↓MMP-2, MMP-9 ↓
MMP9↓,
Wnt↓, AGS cells Lycopene 0.5 μM, 1 μM ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS


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

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,1,   antiOx↑,2,   APC↑,1,   Apoptosis↑,2,   BAX↓,1,   Bax:Bcl2↑,1,   Bcl-2↑,1,   BioAv↓,2,   BioAv↑,2,   Casp3↑,1,   Catalase↑,1,   ChemoSen↑,2,   CHK1↓,1,   Chk2↓,1,   cMyc↓,3,   COX2↓,2,   cycD1↓,2,   cycE↓,2,   DNAdam↓,1,   DNAdam↑,1,   Dose↝,1,   eff↑,1,   ERK↓,1,   p‑ERK↓,1,   GPx↑,2,   GSH↑,1,   p‑GSK‐3β↓,1,   GSR↑,1,   GSTA1↑,1,   IL1↑,1,   IL2↑,1,   IL4↑,1,   IL6↓,1,   Inflam↓,1,   JAK1↓,2,   MMP2↓,1,   MMP7↓,1,   MMP9↓,2,   NF-kB↓,1,   P21↑,2,   P53↓,1,   p65↓,1,   cl‑PARP↑,1,   PCNA↓,1,   PGE2↓,2,   PPARγ↑,1,   Risk↓,2,   ROS↓,4,   SIRT1↑,1,   SOD↑,1,   STAT3↓,2,   TNF-α↓,1,   TNF-α↑,1,   TumCP↓,2,   TumMeta↑,1,   Wnt↓,3,   β-catenin/ZEB1↓,4,   β-TRCP↑,1,   γH2AX↓,1,  
Total Targets: 59

Results for Effect on Normal Cells:
AntiCan↑,1,   antiOx↑,1,   ROS↓,1,  
Total Targets: 3

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
4 Lycopene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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