Database Query Results : Lycopene, , ERK

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


ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
Scientific Papers found: Click to Expand⟱
4794- Lyco,    Anticancer Effect of Lycopene in Gastric Carcinogenesis
- Review, GC, NA
*AntiCan↑, Lycopene from red fruits and vegetables has strong anticancer activity in gastric carcinogenesis.
*ROS↓, As one of the most potent antioxidants, lycopene is effective in decreasing oxidative damage by activating antioxidant enzymes such as GSH, GPx and GST.
*GSH↑,
*GPx↑,
*GSTs↑,
TumCG↓, Lycopene treatment inhibits cancer cell growth and induces apoptosis by suppressing ERK signaling pathway.
Apoptosis↑,
ERK↓,
Bcl-2↓, Lycopene decreases Bcl-2 and increases Bax expression, which induce release of cytochrome C from mitochondria, leading to apoptosis.
BAX↑,
Cyt‑c↑,
TumCCA↑, Lycopene treatment inhibits gastric cancer cell proliferation by increasing cell cycle arrest in G0–G1 phase
*DNAdam↓, Lycopene inhibits H. pylori-induced increases in ROS levels and DNA damage in gastric epithelial cells

4795- Lyco,    Updates on the Anticancer Profile of Lycopene and its Probable Mechanism against Breast and Gynecological Cancer
- Review, BC, NA
TumCG↓, Experimental studies suggest that lycopene can inhibit tumor growth by regulating various signaling pathways for cell growth, arresting the cell cycle, and inducing cell apoptosis.
TumCCA↑,
Apoptosis↑,
P53↝, Lycopene is reported to combat breast cancer specifically via mechanisms, such as regulation of expression of p53 and Bax, suppression of cyclin D
BAX↝,
cycD1↓,
ERK↓, inhibiting the activation of ERK and Akt signaling pathway,
Akt↓,
STAT3↓, and gynecological cancer via various signaling pathways such as STAT3, Nrf2, and NF-κB, down-regulation of ITGB1, ITGA5, FAK, MMP9, and EMT markers, etc.
NRF2↝,
NF-kB↓,
ITGB1↓,
ITGA5↓,
FAK↓,
MMP9↓,
EMT↓,

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

4786- Lyco,    Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines
- in-vitro, BC, MDA-MB-468 - in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3
TumCP↓, dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma.
TumCCA↑,
cl‑PARP↑, demonstrable cleavage of PARP.
ERK↑, Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines
cycD1↓,
P21↓,
p‑Akt↓, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax
mTOR↓,
BAX↑,
AntiCan↑, data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells
Risk↓, Lycopene has been shown to reduce the risk of overall breast cancer more prominently than other carotenoids

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

3264- Lyco,    Pharmacological potentials of lycopene against aging and aging‐related disorders: A review
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*antiOx↑, Anti‐oxidative mechanism of lycopene
*ROS↓, Lycopene inhibits ROS generation and subsequent oxidative stress by inducing antioxidant enzymes (SOD, CAT, GSH, GSH‐Px, and GST) and limiting MDA level and lipid peroxidation (LPO).
*SOD↑,
*Catalase↑,
*GSH↑,
*GSTs↑,
*MDA↓,
*lipid-P↓,
*NRF2↑, Lycopene also prevents ROS release by upregulating Nrf2‐mediated HO‐1 levels and inhibiting iNOS‐activated NO generation
*HO-1↑,
*iNOS↓,
*NO↓,
*TAC↑, upregulating total antioxidant capacity (TAC) and direct inhibition of 8‐OHdG, NOX4.
*NOX4↓,
*Inflam↓, Anti‐inflammatory mechanism of lycopene.
*IL1↓, IL‐1, IL‐6, IL‐8, IL‐1β, and TNF‐α release.
*IL6↓,
*IL8↓,
*IL1β↓,
*TNF-α↓,
*TLR2↓, prevents inflammation by inhibiting toll‐like receptors TLR2 and TLR4 and endothelial adhesion molecules VCAM1 and ICAM‐1.
*TLR4↓,
*VCAM-1↓,
*ICAM-1↓,
*STAT3↓, inhibiting STAT3, NF‐κB, ERK pathway, and IL‐6 and TNF‐α release.
*NF-kB↓,
*ERK↓,
*BP↓, Another clinical study demonstrated that consumption of raw tomato (200 g/day) could prevent type 2 diabetes‐associated cardiovascular diseases by lowering systolic and diastolic blood pressure, upregulating ApoA1, and downregulating ApoB levels
ROS↓, lycopene suppresses the metastasis of the SK‐HEP‐1 cell line by NOX‐4 mRNA expression inhibition and the reactive ROS intracellular activity inhibition
PGE2↓, Lycopene is also used to treat colorectal cancer cells in humans, and the introduction of lycopene decreases the prostaglandin E2 and nitric oxide levels
cardioP↑, Lycopene‐rich foods can be highly beneficial in preventing cardiovascular diseases as lycopene is a potential source of antioxidants
*neuroP↑, beneficial role of lycopene on aging‐related neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, has been confirmed in both experimental and clinical trials
*creat↓, Several pre‐clinical studies reported that lycopene treatment significantly reduced serum urea and serum creatinine, as well as reversed various toxic chemical‐induced nephrotoxicity and oxidative damage by exhibiting excellent antioxidative properti
*RenoP↑,
*CRM↑, its potency in treating aging disorders and its role as a mimic of caloric restriction.


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

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   p‑Akt↓,1,   AntiCan↑,1,   antiOx↑,1,   Apoptosis↑,3,   BAX↓,1,   BAX↑,2,   BAX↝,1,   Bcl-2↓,1,   Bcl-2↑,1,   BioAv↓,2,   BioAv↑,2,   cardioP↑,1,   Casp3↑,1,   Catalase↑,1,   ChemoSen↑,2,   CHK1↓,1,   Chk2↓,1,   cMyc↓,1,   COX2↓,2,   cycD1↓,3,   cycE↓,1,   Cyt‑c↑,1,   DNAdam↓,1,   Dose↝,1,   eff↑,1,   EMT↓,1,   ERK↓,3,   ERK↑,1,   p‑ERK↓,1,   FAK↓,1,   GPx↑,2,   GSH↑,1,   GSR↑,1,   GSTA1↑,1,   IL1↑,1,   IL2↑,1,   IL4↑,1,   IL6↓,1,   Inflam↓,1,   ITGA5↓,1,   ITGB1↓,1,   JAK1↓,1,   MMP2↓,1,   MMP7↓,1,   MMP9↓,3,   mTOR↓,1,   NF-kB↓,2,   NRF2↝,1,   P21↓,1,   P21↑,2,   P53↓,1,   P53↝,1,   p65↓,1,   cl‑PARP↑,2,   PCNA↓,1,   PGE2↓,3,   PPARγ↑,1,   Risk↓,2,   ROS↓,3,   SIRT1↑,1,   SOD↑,1,   STAT3↓,2,   TNF-α↓,1,   TNF-α↑,1,   TumCCA↑,3,   TumCG↓,2,   TumCP↓,2,   TumMeta↑,1,   Wnt↓,2,   β-catenin/ZEB1↓,2,   γH2AX↓,1,  
Total Targets: 72

Results for Effect on Normal Cells:
AntiCan↑,2,   antiOx↑,2,   BP↓,1,   Catalase↑,1,   creat↓,1,   CRM↑,1,   DNAdam↓,1,   ERK↓,1,   GPx↑,1,   GSH↑,2,   GSTs↑,2,   HO-1↑,1,   ICAM-1↓,1,   IL1↓,1,   IL1β↓,1,   IL6↓,1,   IL8↓,1,   Inflam↓,1,   iNOS↓,1,   lipid-P↓,1,   MDA↓,1,   neuroP↑,1,   NF-kB↓,1,   NO↓,1,   NOX4↓,1,   NRF2↑,1,   RenoP↑,1,   ROS↓,3,   SOD↑,1,   STAT3↓,1,   TAC↑,1,   TLR2↓,1,   TLR4↓,1,   TNF-α↓,1,   VCAM-1↓,1,  
Total Targets: 35

Scientific Paper Hit Count for: ERK, ERK signaling
6 Lycopene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:105  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page