Database Query Results : Lycopene, , P53

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

P53, P53-Guardian of the Genome: Click to Expand ⟱

Source: TCGA

Type: Proapototic

TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.

Scientific Papers found: Click to Expand⟱

4780-

Lyco,

Potential inhibitory effect of lycopene on prostate cancer

Review,

Pca,

TumCP↓, Lycopene suppress the progression and proliferation
TumCCA↑, Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions.
Apoptosis↑,
*neuroP↑, the neuro-protective effect of lycopene, mediates the signaling pathways, by inhibiting NF-κB (nuclear factor-κB) and JNK protein (c-Jun N-terminal kinase), and activating Nrf2 (Nuclear factor erythroid 2-related factor 2) and BDNF (
*NF-kB↓,
*JNK↓,
*NRF2↑,
*BDNF↑,
*Ca+2↝, as well as keeping homeostasis by restoring intracellular Ca2+
*antiOx↑, most powerful and natural antioxidants, and its role in preventing prostate cancer.
*AntiCan↑,
*Inflam↓, Anti-inflammatory properties of lycopene depends on time, and it has been found to be through the decrease of inflammatory cytokines (i.e. IL1, IL6, IL8 and tumor necrosis factor-α (TNF-α)
*IL1↓,
*IL6↓,
*IL8↓,
*TNF-α↓,
NF-kB↓, lycopene increased the expression of BCO2 enzyme in an androgen-sensitive cell line that prevented cancer cell proliferation and reduced the NF-κB activity
DNAdam↓, 20 and 50 μM doses of lycopene had an effect on PC3 and DU145 cell lines in inducing apoptosis with DNA damages, and preventing cell growth and colony formation
PSA↓, lycopene twice a day for 3 weeks, showed that lycopene decreases the risk and growth of prostate cancer cells, and also a decrease in the level of PSA,
P53↓, down-regulation of p53, Cyclin-D1, and Nrf-2 have occurred after the incubation of prostate cancer cells with the lycopene received patient’s sera in comparison with placebo
cycD1↓,
NRF2↓,
Akt2↓, treatment with lycopene in PC3 cancer cell lines was associated with down-regulation of AKT2 [
PPARγ↓, Another anti-proliferative effect of lycopene was done by increasing PPARγ-LXRα-ABCA1signaling molecules in protein and mRNA level

4778-

Lyco,

Lycopene exerts cytotoxic effects by mitochondrial reactive oxygen species–induced apoptosis in glioblastoma multiforme

in-vitro,

GBM,

GBM8401

BBB↑, lycopene penetration across the blood-brain barrier and its induction of apoptosis, inhibiting proliferation in GBM8401 and T98G GBM cells
Apoptosis↑,
TumCP↑,
P53↑, lycopene promoted p53 upregulation and suppressed cyclins B and cyclin D, leading to cell cycle arrest through ROS-activated ERK pathways.
CycB↓,
cycD1↓,
TumCCA↓,
mt-ROS↑, Lycopene induced Mito-ROS accumulation in GBM cells
TumCG↓, Lycopene inhibits the cell growth of GBM cells

4797-

Lyco,

A mechanistic updated overview on lycopene as potential anticancer agent

Review,

Var,

AntiCan↑, The anticancer potential of lycopene has been described by various in vitro cells, animal studies, and some clinical trials.
antiOx↓, anticancer potential of lycopene is mainly due to its powerful singlet-oxygen quencher characteristics, simulation of detoxifying/antioxidant enzymes production,
Apoptosis↓, initiation of apoptosis, inhibition of cell proliferation and cell cycle progression as well as modulations of gap junctional communication, the growth factors, and signal transduction pathways
TumCP↓,
TumCCA↑,
Risk↓, The link between increased lycopene consumption and reducedoccurrence of a variety of cancers has been documented by in vitro cells,animal studies, and some clinical studies.
ROS↓, The antioxidant action of lycopene toward ROS
SOD↑, Lycopene can simulate detoxifying/antioxidant enzyme productionsuch as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione reductase.
Catalase↑, . By stimulating ARE system, the lycopene can increase detoxifying/antioxidant enzymes production such as SOD, CAT, GST
GSTs↑,
ARE↑, The upregulating of the ARE system by lycopere has been studied in human BEAS-2B, HepG2, and MCF7
NRF2↑, figure 1
cycD1↓, figure 2
cycE↑,
CDK2↑,
p27↑,
BAX↑,
Bcl-2↓,
P53↑,
ChemoSen↑, Lycopene has also been declared to have a synergistic effect with drugs used in cancer treatment [16,17,27,32]. Lycopene may contribute to improved anticancer effects of enzalutamide

4795-

Lyco,

Updates on the Anticancer Profile of Lycopene and its Probable Mechanism against Breast and Gynecological Cancer

Review,

BC,

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↓,

4791-

Lyco,

Investigating into anti-cancer potential of lycopene: Molecular targets

Review,

Var,

*antiOx↑, Lycopene, the main pigment of tomatoes, possess the strongest antioxidant activity among carotenoids. Lycopene has unique structure and chemical properties.
TumCP↓, the anticancer of lycopene is also considered to be an important determinant of tumor development including the inhibition of cell proliferation, inhibition of cell cycle progression, induction of apoptosis, inhibition of cell invasion, angiogenesis
TumCCA↓,
Apoptosis↑,
TumCI↓,
angioG↓,
TumMeta↓,
*Risk↓, and may be associated with a decreased risk of different types of cancer.
cycD1↓, Several studies suggested lycopene decreased cell cycle related proteins, such as cyclin D1, D3 and E, the cyclin-dependent kinases 2 and 4, bcl-2, while decreased phospho-Akt levels and increased p21, p27, p53 and bax levels and in Bax: Bcl-2 ratio
CycD3↓,
cycE↓,
CDK2↓,
CDK4↓,
Bcl-2↓,
P21↑,
p27↑,
P53↑,
BAX↑,
selectivity↑, lycopene selectively inhibited cell growth in MCF-7 human breast cancer cells but not in the MCF-10 mammary epithelial cells
MMP↓, When treating LNCaP human prostate cancer cells with lycopene, the decreased mitochondrial function could be observed.
Cyt‑c↑, release of mitochondrial cytochrome c and finally led to apoptosis
Wnt↓, Lycopene could inhibit Wnt-TCF signaling pathway in cancer cells.
eff↑, Lycopene could synergistically increase QC anticancer activity and inhibit Wnt-TCF signaling in cancer cells.
PPARγ↑, Lycopene could inhibit the growth of cancer cells by activating the PPARγ – LXRα - ABCA1 pathway and decreasing cellular total cholesterol levels
LDL↓,
Akt↓, Lycopene suppressed Akt activation and non-phosphorylated β-Catenin,
PI3K↓, inhibited the proliferation of colon cancer HT-29 cells, which was associated with suppressing PI3K/Akt/mTOR signaling pathway
mTOR↓,
PDGF↓, Lycopene, however, could inhibit PDGF-BB-induced signaling and cell migration in both human cultured skin fibroblasts and melanoma-derived fibroblasts
NF-kB↓, anticancer properties of lycopene may occur to play its role through the inhibition of the NF-κB signaling pathway
eff↑, lycopene increased the sensitization of cervical cancer cells to cisplatin via the suppression of NF-κB-mediated inflammatory responses, and the modulation of Nrf2-mediated oxidative stress

1715-

Lyco,

Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Review,

Var,

antiOx↑, Carotenoids are well known for their potent antioxidant function in the cellular system.
ROS↑, However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis
ChemoSen↑, when carotenoids are delivered with ROS-inducing cytotoxic drugs, they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants
selectivity↑, In cancer cells with innately high intracellular ROS levels, carotenoids may act as pro-oxidants and trigger ROS-mediated apoptosis of cancer cells.
eff↓, However, under high oxygen tension conditions (e.g., in the lungs of smokers), β-carotene shows tumor-promoting effects.
Casp3↑,
Casp7↑,
Casp9↑,
P53↑,
BAX↑,
DNAdam↑,
mtDam↑, mitochondrial dysfunction
eff↑, Astaxanthin co-treatment with β-carotene and lutein (equimolar 5 µM each)

3275-

Lyco,

Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer

Review,

Var,

TumCCA↑, lycopene impedes the progress of the cell cycle from the G1 to the S phase, primarily by diminishing the cyclin D and cyclin E levels.
cycD1↓,
cycE↓,
CDK2↓, causes a subsequent inactivation of CDK4 and CDK2 through a reduced phosphorylation of Rb
CDK4↓,
P21↑, lycopene elevates CDK inhibitor, p21, and p53 (tumor suppressor) levels
P53↑,
GSK‐3β↓, Finally, GSK3β, p21, p27, Bad, caspase 9, and p53 (via Mdm2) are inactivated
p27↓,
Akt↓, lycopene inhibits AKT (protein kinase B) and mTOR
mTOR↓,
ROS↓, ability of lycopene to minimize ROS formation and mitigate oxidative stress
MMPs↓, lycopene may decrease the activity of metalloproteinases of the matrix and prevent SK-Hep1 cellular adhesion, invasion, and migration
TumCI↓,
TumCMig↓,
NF-kB↓, well-documented that lycopene inhibits NF-kB binding activity
*iNOS↓, They also claimed that the lycopene caused a decline in the LPS-induced protein and mRNA expression of iNOS,
*COX2↓, Lycopene can therefore decrease the gene expression of iNOS and COX-2 as a non-toxic agent via controlling pro-inflammatory genes
lipid-P↓, suppress gastric cancer by multimodal mechanisms of reduction in lipid peroxidation, elevation in the levels of antioxidants, and enhanced GSH
GSH↑,
NRF2↑, Reportedly, lycopene is known to “upregulate” this ARE system via Nrf2 in vitro (HepG2 and MCF-7 cells)

3277-

Lyco,

Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent

Review,

Var,

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: 8

Results for Effect on Cancer/Diseased Cells:
Akt↓,3, Akt2↓,1, angioG↓,1, AntiCan↑,1, antiOx↓,1, antiOx↑,2, Apoptosis↓,1, Apoptosis↑,5, ARE↑,1, BAX↓,1, BAX↑,3, BAX↝,1, BBB↑,1, Bcl-2↓,2, Bcl-2↑,1, BioAv↓,2, BioAv↑,1, Casp3↑,2, Casp7↑,1, Casp9↑,1, Catalase↑,2, CDK2↓,2, CDK2↑,1, CDK4↓,2, ChemoSen↑,3, CHK1↓,1, Chk2↓,1, cMyc↓,1, COX2↓,1, CycB↓,1, cycD1↓,7, CycD3↓,1, cycE↓,3, cycE↑,1, Cyt‑c↑,1, DNAdam↓,2, DNAdam↑,1, Dose↝,1, eff↓,1, eff↑,3, EMT↓,1, ERK↓,2, FAK↓,1, GPx↑,2, GSH↑,2, GSK‐3β↓,1, GSR↑,1, GSTA1↑,1, GSTs↑,1, IL1↑,1, IL2↑,1, IL4↑,1, IL6↓,1, ITGA5↓,1, ITGB1↓,1, JAK1↓,1, LDL↓,1, lipid-P↓,1, MMP↓,1, MMP2↓,1, MMP9↓,2, MMPs↓,1, mtDam↑,1, mTOR↓,2, NF-kB↓,5, NRF2↓,1, NRF2↑,2, NRF2↝,1, P21↑,3, p27↓,1, p27↑,2, P53↓,2, P53↑,5, P53↝,1, p65↓,1, cl‑PARP↑,1, PCNA↓,1, PDGF↓,1, PGE2↓,1, PI3K↓,1, PPARγ↓,1, PPARγ↑,2, PSA↓,1, Risk↓,1, ROS↓,3, ROS↑,1, mt-ROS↑,1, selectivity↑,2, SIRT1↑,1, SOD↑,2, STAT3↓,2, TNF-α↓,1, TNF-α↑,1, TumCCA↓,2, TumCCA↑,4, TumCG↓,2, TumCI↓,2, TumCMig↓,1, TumCP↓,4, TumCP↑,1, TumMeta↓,1, TumMeta↑,1, Wnt↓,2, β-catenin/ZEB1↓,1, γH2AX↓,1,
Total Targets: 105

Results for Effect on Normal Cells:
AntiCan↑,1, antiOx↑,2, BDNF↑,1, Ca+2↝,1, COX2↓,1, IL1↓,1, IL6↓,1, IL8↓,1, Inflam↓,1, iNOS↓,1, JNK↓,1, neuroP↑,1, NF-kB↓,1, NRF2↑,1, Risk↓,1, TNF-α↓,1,
Total Targets: 16

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome

8 Lycopene

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:236  State#:%  Dir#:%
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Database Query Results : Lycopene, , P53

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