Lycopene / NF-kB 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.

Lycopene — a highly lipophilic, acyclic C40 carotenoid (tetraterpene) responsible for the red coloration of tomatoes, watermelon, pink grapefruit, guava, and related foods. It is a non-provitamin-A carotenoid and dietary bioactive rather than an approved anticancer drug. Standard abbreviations include Lyc and LYCO. Tomatoes and processed tomato products are the dominant dietary sources in many populations. Lycopene isomers and oxidative metabolites may differ biologically; circulating and tissue lycopene contains a substantially larger cis-isomer fraction than typical raw tomato sources.

Primary mechanisms (ranked):

  1. Redox modulation: strong singlet-oxygen quenching and antioxidant activity predominate physiologically, while some cancer models show context-dependent mitochondrial ROS generation and pro-oxidant apoptosis.
  2. IGF-1 / PI3K / AKT / mTOR growth signaling suppression, contributing to reduced proliferation and increased apoptosis in multiple experimental cancer models.
  3. Mevalonate / HMG-CoA reductase / Ras signaling suppression, reducing cholesterol synthesis, protein prenylation, Ras membrane localization, and downstream proliferative signaling.
  4. Cell-cycle inhibition through cyclin D1 and other cyclins/CDKs with increased p21/p27 and G0/G1 or other model-dependent arrest.
  5. Intrinsic apoptosis modulation through increased Bax:Bcl-2 ratio, mitochondrial dysfunction, cytochrome-c release, and caspase activation in responsive cancer models.
  6. Anti-inflammatory signaling through suppression of NF-κB, COX-2, IL-6, TNF-α and related inflammatory mediators.
  7. Migration, invasion and EMT suppression involving FAK, MMP2/MMP9, β-catenin, Rho-family signaling and epithelial-mesenchymal transition pathways.
  8. Anti-angiogenic signaling involving VEGF and HIF-1α suppression in selected experimental systems.
  9. NRF2-dependent antioxidant defense is important primarily in normal-cell protection and chemoprevention models; its direction in established cancer is context-dependent rather than uniformly beneficial.

Bioavailability / PK relevance: Oral absorption is formulation- and food-matrix-dependent. Lycopene is lipophilic and incorporation into mixed micelles is improved by dietary fat, disruption of the tomato matrix by processing, and some cis-rich formulations. Human isotope studies indicate substantial interindividual variability and postabsorptive trans-to-cis isomerization. Plasma/tissue persistence is relatively long compared with many phytochemicals, but reported half-life depends strongly on the kinetic model and whether endogenous/background lycopene is being measured.
- tangerine tomato juice has a marked 8.5-fold increase in lycopene bioavailability compared to red tomato juice
- taking with olive oil improves bioavailability. - Lycopene from fresh and unprocessed tomatoes is poorly absorbed by humans. Absorption of lycopene is higher from processed foods such as tomato paste and tomato juice heated in oil.
- cis-isomers of lycopene are more bioavailable than trans-lycopene probably because cis-isomers are more soluble in bile acid micelles.(tomato-based foods contain mainly all-trans-lycopene)
>

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 1–20 µM lycopene, with several mechanistic studies clustering near 2.5–10 µM. Human circulating concentrations after dietary or supplemental intake are generally much lower than the upper concentrations used experimentally; therefore mechanisms demonstrated at high micromolar concentrations should not automatically be assumed achievable in tumors after ordinary oral supplementation. Formulation, food matrix, tissue accumulation and lycopene metabolites further complicate direct concentration comparisons.

Clinical evidence status: RCT / small human / observational evidence, but not established anticancer treatment. Human studies are strongest for biomarker modulation and prostate-related research, while prospective epidemiology generally associates higher dietary or circulating lycopene with modestly lower cancer risk. Trials have not established lycopene as a replacement for standard cancer therapy. Lycopene is used as a food constituent and dietary supplement; FDA GRAS determinations for specified food uses are not anticancer drug approvals.


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 (other ref 5 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↓">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

Lycopene Mechanistic Ranking

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Redox and reactive oxygen species ROS ↓ or ↑ (context-dependent); mt-ROS ↑ in selected models ROS ↓; lipid peroxidation ↓ R–G Redox modulation Antioxidant behavior predominates physiologically, but pro-oxidant mitochondrial ROS-mediated apoptosis occurs in some cancer models. Direction depends on cell type, oxygen tension, dose and lycopene oxidation state.
2 IGF-1 / PI3K / AKT / mTOR IGF-1 signaling ↓; PI3K ↓; AKT ↓; mTOR ↓ ↔ or protective modulation (context-dependent) R–G Growth and survival signaling ↓ One of the most recurrent cancer-relevant signaling clusters; effects vary by tumor model.
3 Mevalonate / HMG-CoA reductase / Ras HMG-CoA reductase ↓; cholesterol synthesis ↓; membrane Ras ↓ LDL/cholesterol regulation ↓ (context-dependent) G Growth signaling and prenylation ↓ Mechanistically important but demonstrated mainly preclinically. Mevalonate can reverse lycopene-induced growth inhibition in experimental cancer cells.
4 Cell-cycle machinery Cyclin D1 ↓; cyclin E ↓; CDK2 ↓; CDK4 ↓; p21 ↑; p27 ↑; arrest ↑ ↔ (generally spared) G Proliferation ↓ Frequently reported downstream consequence of growth-factor, Ras and AKT pathway suppression.
5 Mitochondrial apoptosis Bax:Bcl-2 ↑; MMP ↓; Cyt-c ↑; caspase-9 ↑; caspase-3 ↑; apoptosis ↑ Mitochondrial damage ↓; apoptosis ↓ under oxidative injury R–G Selective death signaling Direction differs markedly by malignant versus stressed normal-cell context.
6 NF-κB inflammatory signaling NF-κB ↓; COX-2 ↓; IL-6 ↓; TNF-α ↓ NF-κB ↓; inflammatory cytokines ↓ R–G Inflammation ↓ Supported across cancer and non-cancer inflammatory models; likely partly secondary to redox and kinase modulation.
7 EMT / FAK / MMP invasion axis EMT ↓; FAK ↓; MMP2 ↓; MMP9 ↓; migration ↓; invasion ↓ ↔ (context-dependent) G Migration and invasion ↓ Relevant mainly to preclinical metastatic phenotypes rather than demonstrated clinical antimetastatic efficacy.
8 Wnt / β-catenin / STAT3 Wnt ↓; β-catenin ↓; JAK1 ↓; STAT3 ↓ ↔ (context-dependent) G Proliferative transcription ↓ Observed in several epithelial cancer models but not established as a universal primary target.
9 VEGF / HIF-1α angiogenesis VEGF ↓; HIF-1α ↓; angiogenesis ↓ ↔ or angiogenic signaling ↓ (context-dependent) G Angiogenesis ↓ Predominantly preclinical evidence.
10 NRF2 / antioxidant response NRF2 ↑ or ↓ (context-dependent) NRF2 ↑; HO-1 ↑; NQO1 ↑; SOD ↑; GSH defense ↑ R–G Stress defense ↑ NRF2 activation is well supported in protective normal-tissue models. In established cancer, NRF2 biology is dual-sided and should not be represented as uniformly anticancer.
11 DNA damage and genomic protection DNA damage ↑ or ↓ (model-dependent); p53 ↑ Oxidative DNA damage ↓ G Context-dependent genomic modulation Normal-cell chemoprevention and cancer-cell killing can produce opposite apparent directions.
12 Glycolysis and metabolic signaling Glycolysis ↓ (limited evidence); c-Myc ↓; G6PD ↓ ↔ G Metabolic growth support ↓ Evidence is substantially less developed than for AKT, cell cycle or redox pathways; should remain secondary.
13 Chemosensitization Sensitivity ↑ (drug- and model-dependent) Chemotoxicity may ↓ in protective models G Adjunct response modulation Preclinical sensitization has been reported, including androgen-axis therapies; simultaneous cytoprotection is also reported with some cytotoxic agents, so interaction cannot be generalized.
14 Radiosensitivity and radioprotection ↔ or sensitivity ↑ (model-dependent) Radioprotection ↑ in some models G Context-dependent radiation interaction Evidence supports both antioxidant radioprotection and experimental radiosensitization depending on system; clinical significance remains uncertain.
15 Clinical Translation Constraint Oral tumor exposure uncertain Generally well tolerated at nutritional and commonly studied supplemental exposure G Translation limited Low and variable oral bioavailability, food-matrix effects, nonlinear dose-exposure relationships, uncertain tumor concentrations, and limited adequately powered cancer RCTs constrain translation of high-concentration in-vitro mechanisms.

TSF: P: 0–30 min    R: 30 min–3 hr    G: >3 hr



Alzheimer’s disease relevance: Lycopene has meaningful preclinical AD relevance but no established clinical efficacy. Cell and animal models report reduced oxidative stress and neuroinflammation, improved mitochondrial function, suppression of BACE1 and amyloidogenic signaling, reduced Aβ burden, attenuation of tau hyperphosphorylation, and preservation of BDNF/synaptic signaling. Human evidence remains insufficient to classify lycopene as an AD treatment.

Translation status: Preclinical only for disease-modifying AD mechanisms. Computational, cellular, rodent and formulation studies support biological plausibility, but clinical supplementation studies have not demonstrated prevention or treatment of Alzheimer’s disease.

Lycopene in Alzheimer’s Disease Models

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Oxidative stress / NRF2 ROS ↓; NRF2 ↑; antioxidant defense ↑ Oxidative neuronal injury ↓ One of the most consistent effects in cellular and animal neurotoxicity models.
2 Amyloid / BACE1 BACE1 ↓; Aβ ↓ Amyloidogenic processing ↓ Supported experimentally; no demonstrated disease-modifying effect in humans.
3 Neuroinflammation / NF-κB NF-κB ↓; TNF-α ↓; IL-1β ↓; IL-6 ↓ Neuroinflammation ↓ Reported in several Aβ and inflammatory animal models.
4 Mitochondrial function mt-ROS ↓; MMP preserved; mitochondrial damage ↓ Bioenergetic integrity ↑ Consistent with antioxidant and anti-apoptotic neuronal effects.
5 Tau phosphorylation Hyperphosphorylated tau ↓ Tau pathology ↓ Demonstrated in transgenic mouse models; human relevance remains unproven.
6 BDNF / synaptic plasticity BDNF ↑; TrkB signaling ↑ Synaptic resilience ↑ Preclinical evidence suggests preservation of learning/memory pathways.
7 Neuronal apoptosis Bax:Bcl-2 ↓; Cyt-c ↓; caspase-3 ↓ Neuronal survival ↑ Predominantly secondary to redox, mitochondrial and inflammatory modulation.


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
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/CCND1↓,
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, NA
*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/CCND1↓, 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/CCNE↓,
CDK2↓,
CDK4↓,
Bcl-2↓,
P21↑,
p27/CDKN1B↑,
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.
Synergy↑, 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
ChemoSen↑, 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

4789- Lyco,    Inhibitory Effect of Lycopene on Amyloid-β-Induced Apoptosis in Neuronal Cells
- in-vitro, AD, SH-SY5Y
*antiOx↑, Lycopene is an antioxidant protecting from oxidative stress-induced cell damage
*ROS↓, Lycopene inhibited apoptosis by reducing ROS, and by inhibiting mitochondrial dysfunction and NF-κB-target gene Nucling expression in neuronal cells.
*NF-kB↓,
*neuroP↑, Lycopene may be beneficial for preventing oxidative stress-mediated neuronal death in patients with neurodegeneration.
*MMP↓, As shown in Figure 3C, amyloid-β increased the ratio of green to red fluorescence in the cells, which reflects a decrease in MMP in amyloid β-stimulated cells
*mtDam↓, Lycopene suppressed decrease in OCR in amyloid-β-stimulated cell, suggesting that lycopene prevents mitochondrial damage induced by amyloid-β in the cells.
*OCR↓, In the present study, lycopene significantly inhibited amyloid-β-induced mitochondrial dysfunction, which was proven by its protective effect in reducing both MMP and OCR.

4801- Lyco,    Lycopene in the Prevention of Cardiovascular Diseases
- Review, CardioV, NA
*BioAv↝, Taking into account the fact that humans are not able to synthesize lycopene de novo, therefore its supply with food is necessary to take advantage of its pro-health properties.
*cardioP↑, protective effect on cardiovascular diseases
*BioAv↑, It is assumed that thanks to the cis form, lycopene is highly bioavailable in the human diet
*BioAv↑, bioavailability of lycopene as a result of its trans to cis isomerization can be achieved by adding fish oil or olive oil to tomato dishes.
*antiOx↑, Antioxidant Effects of Lycopene
*ROS↓, Lycopene is a highly effective antioxidant that, due to the high reactivity between the long polyene chain and free radicals, enables the elimination of singlet oxygen and the reduction of reactive oxygen species (ROS)
*ARE↑, activating the antioxidant response element (ARE)
*SOD↑, it increases the amount of antioxidant enzymes, which include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*lipid-P↓, figure 3
*COX2/PTGS2↓, lycopene (in the form of watermelon powder) reduced inflammation by reducing the activity of the pro-inflammatory mediator cyclooxygenase 2 (COX-2),
*Inflam↓, Anti-Inflammatory Mechanism of Lycopene
*IL1β↓, inhibits the synthesis and release of pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α.
*IL6↓,
*IL8↑,
*TNF-α↓,
*NF-kB↓, inhibition of the nuclear factor κB (NF-κB)
*BP↓, 15 or 30 mg of lycopene was associated with a significant reduction in systolic BP

4785- Lyco,    The Protective Anticancer Effect of Natural Lycopene Supercritical CO2 Watermelon Extracts in Adenocarcinoma Lung Cancer Cells
- in-vitro, Lung, A549
ROS↑, we found that Lyc W significantly increased the spontaneous release of ROS
NF-kB↑, We found that Lyc W significantly increased the nuclear expression of NF-kB in comparison to medium (p = 0.0289) and to Lyc G, Lyc T and Lyc S treatments
Apoptosis↑, Lyc W Induces Cell Apoptosis

4784- Lyco,    Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives
- Review, Diabetic, NA - Review, CardioV, NA
*antiOx↑, Owing to its potent antioxidant properties, lycopene can potentially alleviate enhanced levels of proinflammatory mediators (e.g., proinflammatory cytokines IL-8, -6, and -1, and oxidized phospholipids) and prevent NF-κB activation
*IL8↓,
*IL6↓,
*IL1↓,
*NF-kB↓,
Inflam↓, graphical abstract
cycD1/CCND1↓,
MMP2↓,
MMP9↓,
Bcl-2↓,
NF-kB↓,
*Nrf1↑, normal cells
*antiOx↑,
*BDNF↑,
*neuroP↑,
*cardioP↑,
ROS↑, i) enhanced oxidative stress due to prooxidant activities of lycopene under circumstances of tumor cell
Dose↝, There are no known adverse effects from low (12 mg/day) to very high (150 mg/day) intake of dietary or formulated lycopene in a healthy population

4782- Lyco,    New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene
- Review, Var, NA
AntiCan↑, From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer.
TumCP↓, Lycopene was known to be able to suppress cancerous cell proliferation, migration, invasion and adhesion activity in cell culture studies.
TumCMig↓,
TumCI↓,
TumCA↓,
ROS↓, Such suppression was often observed with changes of cancer-related gene expression and relief of oxidative stress
MMP2↓, In general, lycopene could suppress the expression of MMP-2, MMP-7, MMP-9, Sp1, IGF-1R, VEGF while increasing E-cadherin stabilization, connexin 43, nm23-H1, TIMP-1 and TIMP-2 levels
MMP7↓,
MMP9↓,
VEGF↓,
E-cadherin↑,
TIMP1↑,
TIMP2↑,
BioAv↝, it is recommended to avoid consumption of lycopene concurrently with high dietary fiber intake as several types of dietary fiber were found to be able to reduce the bioavailability of lycopene
*IL12↓, lycopene could suppress proinflammatory cytokines such as IL-12, TNF-α, IL-1, IL-1β, IL-6
*TNF-α↓,
*IL1↓,
*IL1β↓,
*IL6↓,
COX2/PTGS2↓, Sprague Dawley rat model, lycopene treatment after induction by azoxymethane caused suppression of aberrant crypt foci, preneoplastic lesion and biomarkers such as COX-2 and iNOS expression
iNOS↓,
*radioP↑, lycopene before induction of DNA damage via X-irradiation as lycopene treatment after irradiation failed to show such DNA protective effect
NF-kB↓, anti-cancer effect of lycopene was also observed in pancreatic cancer cells (PANC-1 cell line) whereby significant reduction of ROS, NF-κB and anti-apoptotic biomarkers (cIAP1, cIAP2 and survivin) was detected while an increment of caspase-3 and Bax:
survivin↓,
Casp3↑,
Bax:Bcl2↑,

4780- Lyco,    Potential inhibitory effect of lycopene on prostate cancer
- Review, Pca, NA
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/CCND1↓,
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

4779- Lyco,    Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells
- in-vitro, PC, PANC1
ROS↓, The results show that the lycopene decreased intracellular and mitochondrial ROS levels, mitochondrial function (determined by the mitochondrial membrane potential and oxygen consumption rate),
NF-kB↓, NF-κB activity, and expression of NF-κB-dependent survival genes in PANC-1 cells.
tumCV↓, Lycopene reduced cell viability with increases in active caspase-3 and the Bax to Bcl-2 ratio in PANC-1 cells
Casp3↑,
Apoptosis↑, Lycopene Induces Apoptosis in PANC-1 Cells
OCR↓, Lycopene Decreases Intracellular and Mitochondrial ROS Levels and OCR in PANC-1 Cells
MMP↓, Lycopene Decreases MMP in PANC-1 Cells
CIP2A↓, Lycopene Decreases Expression of cIAP1, cIAP2, and Survivin in PANC-1 Cells
survivin↓,
Casp3↑, Thus, lycopene induces caspase-3-dependent apoptosis and increased the Bax to Bcl-2 ratio in PANC-1 cells.
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↑, Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables.
tumCV↓, Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio)
DNAdam↑,
Apoptosis↑,
cl‑Casp3↑,
cl‑Casp9↑,
Bax:Bcl2↑,
ROS↓, Lycopene reduced the level of intracellular and mitochondrial ROS
NF-kB↓, attenuation of the DNA-binding activity of NF-κB p50/p50 and the level of COX-2 gene expression.
COX2/PTGS2↓,
EGFR↓, Lycopene Reduces ROS Levels and Inhibits EGFR/Ras/ERK and p38 MAPK Signaling in AGS Cells
p38↓,

8421- Lyco,    Lycopene: Sojourn from kitchen to an effective therapy in Alzheimer's disease
- Review, AD, NA
*neuroP↑, Lycopene has established itself as a promising therapy for AD owing to its neuroprotective activities, including antioxidant, anti-inflammatory, and antiamyloidogenic properties
*antiOx↑,
*Inflam↓,
*AntiMyl↑,
*ROS↓, Lycopene is reported to be the most potent molecule among natural carotenoids in its ability to scavenge free radicals.
*MMP↑, # ROS generation and restored mitochondrial membrane potential
*NGF↑, " secretion of growth factors (NGF, BDNF and VEGF),
*BDNF↑,
*VEGF↑,
*Aβ42↓, lower β-amyloid1-42 levels due to downregulation of β-amyloid precursor protein,
*PI3K↑, activating PI3K/Akt/Nrf2 signaling
*Akt↑,
*NRF2↑,
*lipid-P↓, Lycopene mitigated lipid peroxidation and restored the levels of antioxidant defense as reduced GSH, CAT, and SOD.
*GSH↑,
*Catalase↑,
*SOD↑,
*cognitive↑, lycopene (2.5 and 5 mg/kg for 21 days) has been reported to significantly improve colchicine-induced cognitive dysfunction
*Learn↑, In another study, long-term lycopene administration at higher doses (5 and 10 mg/kg p.o. for 15 days) improved the learning ability and retention of learned memory in scopolamineinduced amnesic mice
*memory↑,
*APP↓, Lycopene suppressed the expression of APP and β-secretase 1, and elevated the expression of A Disintegrin and Metalloprotease 10 (ADAM10), thereby inhibited the β-amyloid accumulatio
*BACE/β-secretase↓,
*ADAM10↑,
*NF-kB↓, Furthermore, neuroprotective effect of lycopene is attributed to modulation of Nrf2 signaling and NF-κB translocation in cell model, thereby ameliorate cognitive impairment
*AChE↓, attenuated elevated MDA, AChE
*MAOA↓, lower MAO activity,
*BioAv↝, bioactivity or bioavailability (1030% of dietary administrated).

8414- Lyco,    Exploring the Therapeutic Potential of Lycopene: Mechanisms, Biological Activities, and Health Benefits
- Review, Var, NA - Review, AD, NA
*ROS↓, regulation of oxidative stress, inflammation
*Inflam↓,
*hepatoP↑, Its role containing nephroprotective, hepatoprotective, cardioprotective, and neuroprotective properties, anti-arthritis, anti-obesity, and wound healing has been documented
*cardioP↑,
*neuroP↑,
*AntiArt↑,
*Obesity↓,
*Wound Healing↑,
*BioAv↑, potential of emerging nanoformulation strategies to improve its bioavailability and therapeutic efficacy in disease management.
*GSTs↑, In TD-challenged rats, hepatic activities and gene expression of glutathione S-transferase (GST), thioredoxin-1 (Txn-1), superoxide dismutase (SOD), and catalase (CAT) were decreased; these changes were mitigated by lycopene.
*Trx1↑,
*SOD↑,
*Catalase↑,
*ALAT↓, 5 mg/kg b.w led to partial, dose-dependent improvements in ALT, LDH, AST, and MDA levels
*LDH↓,
*AST↓,
*MDA↓,
*cognitive↑, Lycopene has also been reported to reduce neuronal damage, inhibit oxidative stress, and improve cognitive function in various experimental models.
*memory↑, chronic lycopene administration caused an improvement in memory retention, reducing neuroinflammation
*NeuroI↓,
*Aβ↓, The lycopene administration was found to reduce Aβ accumulation, increase the LRP1 levels, and reduce the RAGE levels in the cerebrospinal fluid or the choroid plexus.
*LRP1↑,
*RAGE↓,
*NRF2↑, lycopene exerts a protective role against global ischemic brain injury through its activation of the Nrf2/HO-1 signaling pathway and anti-apoptotic properties
*HO-1↑,
tumCV?, lycopene significantly decreases cell viability by increasing the Bax/Bcl-2 ratio and promoting DNA fragmentation.
Bax:Bcl2↑,
DNAdam↑,
Apoptosis↑, lycopene induces apoptosis through suppressing β-catenin-c-myc/cyclin D1 axis and reducing ROS levels.
β-catenin/ZEB1↓,
cMyc↓,
cycD1/CCND1↓,
ROS↓,
TumCCA↑, Lycopene plays a substantial role in inhibition of cancer cell growth by causing cell cycle arrest.
Akt↓, Lycopene treatment suppressed Akt activation as well as non-phosphorylated β-catenin protein level
*Synergy↑, The results showed that even at low concentrations, lycopene and EPA worked synergistically to inhibit cancer cell proliferation.
*MDA↓, important reduction in colon tissue L-MDA and down-regulation of NF-κB, TGF-β1, caspase-3, in addition to a noticeable increase in CAT activity and GSH concentration, and up-regulation of Bcl-2 and IL-10 were detected after lycopene treatment
*NF-kB↓,
*TGF-β↓,
*Casp3↓,
*Catalase↑,
*GSH↑,
*Bcl-2↑,
*IL10↑,
*MUC1↑, It enhances mucin production, contributing to improved mucosal barrier function.
*IBI↑,
*RenoP↑, lycopene as renoprotective was confirmed through different mechanisms
*ChemoSen↑, lycopene enhances the sensitivity of cervical cancer cells to cisplatin by downregulating Bcl-2 expression, upregulating Bax expression and reducing cell viability
*Synergy↑, Curcumin Effect on benign prostatic hyperplasia ° The combination treatment attenuated prostate hyperplasia and alleviated BPH pathological features.
*Synergy↑, lycopene, given together with methotrexate, improved serum urea, creatinine levels, reduced oxidative damage markers, and suggestively reversed structural changes in kidney tissue
*BMD↑, It was noticed that substantial bone density loss was not noticed in women taking the tomato sauce, whereas the control group had bone loss.

8407- Lyco,    Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines
- in-vitro, Pca, LNCaP
CholSyn↓, lycopene treatment (2.5-10 μM) dose dependently reduced intracellular total cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and by inactivating Ras
HMGCR↓,
RAS↓,
NF-kB↓, lycopene reduced the Ras-dependent activation of nuclear factor-kappaB (NF-κB)
ROS↓, ycopene significantly reduced ROS production in a dose-dependent manner, starting the inhibition at the concentration of 2.5 uM
p‑Jun↓, Such a reduction was parallel to an inhibition of reactive oxygen species production and to a decrease in the phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and p38.
TumCCA↑, These effects were also accompanied by an arrest of cell cycle progression and by apoptosis induction
Apoptosis↑,
cycD1/CCND1↓, as evidenced by a decrease in cyclin D1 and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in Bax:Bcl-2 ratio.
p‑Akt↓,
P21↑,
p27/CDKN1B↑,
P53↑,
Bax:Bcl2↑,

4228- Lyco,    A review for the pharmacological effect of lycopene in central nervous system disorders
- Review, AD, NA - Review, Park, NA
*cognitive↑, Lycopene also improves cognition and memory ability of rodents in different pathological conditions, such as diabetes, colchicine exposure, high-fat diet (HFD), and aging.
*memory↑,
*Inflam↓, inhibition of oxidative stress and neuroinflammation, inhibition of neuronal apoptosis, and restoration of mitochondrial function have been shown to mediate the neuroprotective effects of lycopene.
*Apoptosis↓,
*ROS↓,
*neuroP↑,
*NF-kB↓, inhibition of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), activation of the nuclear factor erythroid 2-related factor (Nrf2) and brain-derived neurotrophic factor (BDNF) signaling, and restoration of intracellular Ca2+ homeostasis,
*JNK↓,
*NRF2↑,
*BDNF↑,
*MDA↓, 8 weeks of lycopene treatment (5 mg/kg) has been shown to reverse malondialdehyde (MDA) increase and glutathione peroxidase (GSH-Px) decrease in serum in tau transgenic mice expressing P301 L mutation
*GPx↑,

4800- Lyco,    Recent insights on pharmacological potential of lycopene and its nanoformulations: an emerging paradigm towards improvement of human health
- Review, Var, NA
*antiOx↑, It is a potent antioxidant and free radical scavenger owing to the presence of 13 carbon–carbon double bonds, out of which 11 are conjugated and the remaining 2 are non-conjugated.
Keap1↝, many biological effects on different types of cancers like prostate, breast, skin, and oral cancer by targeting the Keap1-NF-kB, Keap1-Nrf 2 and PI3K/AKT/m-TOR signalling pathway.
NF-kB↝,
NRF2↝,
PI3K↝,
Akt↝,
mTOR↝,
*GutMicro↑, lycopene also has the ability to modify the gut microbiome

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.

3262- Lyco,    Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1
- in-vitro, adrenal, SK-HEP-1
TumCI↓, lycopene (1–10 μM) significantly inhibited SK-Hep-1 invasion (P<.05) and that this effect correlated with the inhibition of MMP-9 at the levels of enzyme activity
MMP9↓,
NF-kB↓, Lycopene also significantly inhibited the binding abilities of NF-κB and Sp1 and decreased, to some extent, the expression of insulin-like growth factor-1 receptor (IGF-1R) and the intracellular level of reactive oxygen species
Sp1/3/4↓,
IGF-1R↓,
i-ROS↓,

3261- Lyco,    Lycopene and Vascular Health
- Review, Stroke, NA
*Inflam↓, main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabolic profile, and reduce arterial stif
*antiOx↑, It is a much more potent antioxidant than alpha-tocopherol (10 × more potent) or beta-carotene (twice as potent)
*AntiAg↑, lycopene, protecting against myocardial infarction and stroke, is its antiplatelet activity
*cardioP↑, favorable effect in patients with subclinical atherosclerosis, metabolic syndrome, hypertension, peripheral vascular disease, stroke and several other cardiovascular disorders
*SOD↑, Lycopene modulates also the production of antioxidant enzymes, such as superoxide dismutase and catalase
*Catalase↑,
*ROS↓, By reducing oxidative stress and reactive oxygen species, lycopene increases the bioavailability of nitric oxide (NO), improves endothelium-dependent vasodilation and reduces protein, lipids, DNA, and mitochondrial damage (
*mtDam↓,
*cardioP↑, Lycopene exerts a cardioprotective effect against atrazine induced cardiac injury due to its anti-inflammatory effect, by blocking the NF-kappa B pathway and NO production
*NF-kB↓,
*NO↓,
*COX2/PTGS2↓, downregulation of cyclooxygenase 2,
*LDL↓, significant reductions in total and LDL cholesterol were revealed only at doses of, at least, 25 mg lycopene/day
*Synergy↑, It was noticed that lycopene can potentiate the antiplatelet effect of aspirin, which requires low lycopene diet
*ER Stress↓, Lycopene protects the cardiomyocytes by relieving ERS
*BioAv↑, Lycopene is very bioavailable in the presence of oil, especially in monounsaturated oils, other dietary fats and processed tomato products
*Synergy↑, Lycopene can increase the antioxidant properties of vitamin C, E, polyphenols and beta-carotene in a synergistic way
*MMPs↓, figure 3, secretion of MMPs
*COX2/PTGS2↓,
*RAGE↓,

1708- Lyco,    The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies
- Review, Var, NA
OS↑, reduced prostate cancer-specific mortality in men at high risk for prostate cancer
ChemoSen↑, improved the response to docetaxel chemotherapy in advanced castrate-resistant prostate cancer
QoL↑, lycopene improved the quality of life, and provided relief from bone pain and control of lower urinary tract symptoms
PSA∅, PSA stabilisation in prostate cancer
Synergy↑, Lycopene co-supplementation with vitamin E also showed an improvement in the results of prostate cancer treatment
AntiCan↑, lycopene intake showed a strong protective effect against stomach cancer, regardless of H. pylori status
AntiCan↑, A lycopene-rich diet was shown to reduce the incidence of pancreatic cancer in humans by 31%
angioG↓,
VEGF↓,
Hif1a↓,
SOD↑,
Catalase↑,
GPx↑,
GSH↑,
GPx↑,
GR↑,
MDA↓,
NRF2↑,
HO-1↑,
COX2/PTGS2↓,
PGE2↓,
NF-kB↓,
IL4↑,
IL10↑,
IL6↓,
TNF-α↓,
PPARγ↑,
TumCCA↑, G(0)/G(1) phase
FOXO3↓,
Casp3↑,
IGF-1↓, breast cancer,crc
p27/CDKN1B↑,
STAT3↓,
CDK2↓,
CDK4↓,
P21↑,
PCNA↓,
MMP7↓,
MMP9↓,

3528- Lyco,    The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene
- Review, Nor, NA - Review, AD, NA - Review, Park, NA
*antiOx↑, the antioxidant effect of lycopene
*ROS↓, Lycopene has the ability to reduce reactive oxygen species (ROS) and eliminate singlet oxygen, nitrogen dioxide, hydroxyl radicals, and hydrogen peroxide
*BioAv↝, human body cannot synthesize lycopene. It must be supplied with the diet
*Half-Life↑, half-life of lycopene in human plasma is 12–33 days
*BioAv↓, bioavailability decreases with age and in the case of certain diseases
*BioAv↑, heat treatment process of food increases the bioavailability of lycopene
*cardioP↑, positive effect on cardiovascular diseases, including the regulation of blood lipid levels
*neuroP↑, beneficial effects in nervous system disorders, including neurodegenerative diseases such as Parkinson′s disease and Alzheimer′s disease
*H2O2↓, Lycopene has the ability to reduce reactive oxygen species (ROS) and eliminate singlet oxygen, nitrogen dioxide, hydroxyl radicals, and hydrogen peroxide
*VitC↑, ability to regenerate non-enzymatic antioxidants such as vitamin C and E.
*VitE↑,
*GPx↑, increase in cardiac GSH-Px activity and an increase in cardiac GSH levels
*GSH↑,
*MPO↓, also a decrease in the level of cardiac myeloperoxidase (MPO), cardiac H2O2, and a decrease in cardiac glutathione S transferase (GSH-ST) activity.
*GSTs↓,
*SOD↑, increasing the activity of GSH-Px and SOD in the liver
*NF-kB↓, reducing the expression of NF-κB mRNA in the heart
*IL1β↓, decreased the level of IL-1β and IL-6 and increased the level of anti-inflammatory IL-10 in the heart
*IL6↓,
*IL10↑,
*MAPK↓, inhibited the activation of the ROS-dependent pro-hypertrophic mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways.
*Akt↓,
*COX2/PTGS2↓, decrease in the levels of pro-inflammatory mediators in heart: COX-2, TNF-α, IL-6, and IL-1β and an increase in the anti-inflammatory cardiac TGF-β1.
*TNF-α↓,
*TGF-β1↑,
*NO↓, reduced NO levels in heart and cardiac NOS activity
*GSR↑, increase in the level of cardiac and hepatic SOD, CAT, GSH, GPx, and glutathione reductase (GR)
*NRF2↑, It also activated nuclear factor-erythroid 2 related factor 2 (Nrf2). This affected the downstream expression of HO-1 [97].
*HO-1↑,
*TAC↑, Researchers observed an increase in the liver in TAC and GSH levels and an increase in GSH-Px and SOD activity
*Inflam↓, study showed that lycopene was anti-inflammatory
*BBB↑, Lycopene is a lipophilic compound, which makes it easier to penetrate the blood–brain barrier.
*neuroP↑, Lycopene had also a neuroprotective effect by restoring the balance of the NF-κB/Nrf2 pathway.
*memory↑, lycopene on LPS-induced neuroinflammation and oxidative stress in C57BL/6J mice. The tested carotenoid prevented memory loss

3278- Lyco,    Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells
- in-vitro, Colon, SW480
TNF-α↓, In cells treated with lycopene and LPS, the mRNA expression of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner
IL1β↓,
IL6↓,
iNOS↓,
COX2/PTGS2↓,
PGE2↓, The concentrations of PGE2 and NO decreased according to the lycopene concentration
NO↓,
NF-kB↓, The protein expressions of NF-κB and JNK were decreased significantly according to lycopene concertation
JNK↓,
Inflam↓, Lycopene was found to have anti-inflammatory effects in a rat model
MPO↓, decreased myeloperoxidase (MPO) activity, as a marker of inflammation,

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/PTGS2↓,
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/CCNE↓,
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/CCND1↓,
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

3275- Lyco,    Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer
- Review, Var, NA
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/CCND1↓,
cycE/CCNE↓,
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/CDKN1B↓,
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/PTGS2↓, 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)

3268- Lyco,    Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders
- Review, AD, NA
*BioAv↓, Lycopene bioavailability can be decreased by ageing, and some of the pathological states, such as cardiovascular diseases (CVDs)
*AntiCan↑, For instance, it has been shown that a higher dietary intake and circulating concentration of lycopene have protective effects against prostate cancer (PCa), in a dose-dependent way
*ROCK1↓, It remarkably lessened the expression of ROCK1, Ki-67, ICAM-1 and ROCK2,
*Ki-67↓,
*ICAM-1↓,
*cardioP↑, Lycopene is a cardioprotective nutraceutical.
*antiOx↑, Lycopene is a well-known antioxidant.
*NQO1↑, Furthermore, lycopene supplementation improves mRNA expressions of the NQO-1 and HO-1 as antioxidant enzymes.
*HO-1↑,
*TNF-α↓, downregulate inflammatory cytokines (i.e., TNF-α, and IL-1β) in the hippocampus of the mice.
*IL22↓,
*NRF2↑, Lycopene decreased neuronal oxidative damage by activating Nrf2, as well as by inactivating NF-κB translocation in H2O2-related SH-SY5Y cell model
*NF-kB↓,
*MDA↓, significantly reduced the malondialdehyde (MDA)
*Catalase↑, Furthermore, it improved the catalase (CAT), superoxide dismutase (SOD), and GSH levels, and antioxidant capacity [109].
*SOD↑,
*GSH↑,
*cognitive↑, Lycopene administration considerably improved cognitive defects, noticeably reduced MDA levels and elevated GSH-Px activity, and remarkably reduced tau
*tau↓,
*hepatoP↑, Lycopene was also found to be effective against hepatotoxicity by acting as an antioxidant, regulating total glutathione (tGSH) and CAT concentrations
*MMP2↑, It also elevated MMP-2 down-regulation
*AST↓, lowering the liver enzymes levels, like aspartate transaminase (AST), alanine transaminase (ALT), LDL, free fatty acid, and MDA.
*ALAT↓,
*P450↑, Moreover, tomato powder has been shown to have a protective agent against alcohol-induced hepatic injury by inducing cytochrome p450 2E1
*DNAdam↓, lycopene decreased DNA damage
*ROS↓, It has been revealed that they inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity in rats’ liver
*neuroP↑, lycopene consumption relieved cognitive defects, age-related memory loss, neuronal damage, and synaptic dysfunction of the brain.
*memory↑,
*Ca+2↓, Lycopene suppressed the 4-AP-invoked release of glutamate and elevated intra-synaptosomal Ca2+ level.
*Dose↝, an in vivo study revealed that lycopene (6.5 mg/day) was effective against cancer in men [147]. However, lycopene dose should be increased up to 10 mg/day, in the case of advanced PCa.
*Dose↑, lycopene supplementation (15 mg/day, for 12 weeks) in an old aged population improved immune function through increasing natural killer cell activity by 28%
*Dose↝, Finally, according to different epidemiological studies, daily lycopene intake can be suggested to be 2 to 20 mg per day
*toxicity∅, A toxicological study on rats showed the no-observed-adverse-effect level at the highest examined dose (i.e., 1.0% in the diet)
PGE2↓, Lycopene doses of 0, 10, 20, and 30 µM were used to treat human colorectal cancer cell. Prostaglandin E2 (PGE2), and NO levels declined after lycopene administration,
CDK2↓, Treatment with lycopene reduced cell hyperproliferation induced by UVB and ultimately promoted apoptosis and reduced CDK2 and CDK4 complex in SKH-1 hairless mice
CDK4↓,
STAT3↓, lycopene reduced the STAT3 expression in ovarian tissues
NOX↓, (SK-Hep-1) cells and indicated a substantial reduction in NOX activity. Moreover, it inhibits the protein expression of NOX4, NOX4 mRNA and ROS intracellular amounts
NOX4↓,
ROS↓,
*SREBP1/SREBF1↓, Lycopene decreases the fatty acid synthase (FAS), sterol regulatory element-binding protein 1c (SREBP-1c), and Acetyl-CoA carboxylase (ACC1) expression in HFD mice.
*FASN↓,
*ACC↓,

3534- QC,  Lyco,    Synergistic protection of quercetin and lycopene against oxidative stress via SIRT1-Nox4-ROS axis in HUVEC cells
- in-vitro, Nor, HUVECs
*ROS↓, especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production.
*NOX4↓, Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress
*Inflam↓, quercetin-lycopene combination downregulated inflammatory genes induced by H2O2, such as IL-17 and NF-κB.
*NF-kB↓, NF-κB p65 was activated by H2O2 but inhibited by the quercetin-lycopene combination.
*p65↓,
*SIRT1↑, quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity
*cardioP↑, The cardioprotective role of SIRT1
*IL6↓, LYP: Q = 1:5), interacted with deacetylase SIRT1 to inhibit NF-κB p65 and Nox4 enzyme, downregulated inflammatory cytokines such as IL-6 and pro-inflammatory enzymes such as COX-2, and suppressed ROS elevation activated by H2O2.
*COX2/PTGS2↓,


Showing Research Papers: 1 to 25 of 25

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 4,   GSH↑, 3,   GSR↑, 1,   HO-1↑, 1,   Keap1↝, 1,   lipid-P↓, 1,   MDA↓, 1,   MPO↓, 1,   NOX↓, 1,   NOX4↓, 1,   NRF2↓, 1,   NRF2↑, 2,   NRF2↝, 2,   ROS↓, 9,   ROS↑, 2,   i-ROS↓, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

CholSyn↓, 1,   GSK‐3β↓, 1,   LDL↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 9,   BAX↓, 1,   BAX↑, 1,   BAX↝, 1,   Bax:Bcl2↑, 5,   Bcl-2↓, 2,   Bcl-2↑, 1,   Casp3↑, 5,   cl‑Casp3↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   iNOS↓, 2,   p38↓, 1,   survivin↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 4,   Akt↝, 1,   p‑Akt↓, 1,   Akt2↓, 1,   CIP2A↓, 1,   EGFR↓, 1,   ERK↓, 2,   IGF-1R↓, 1,   JAK1↓, 1,   JNK↓, 1,   mTOR↓, 2,   mTOR↝, 1,   PI3K↓, 1,   PI3K↝, 1,   RAS↓, 1,   Sp1/3/4↓, 1,   STAT3↓, 4,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 2,   FOXO3↓, 1,   tumCV?, 1,   tumCV↓, 2,  

DNA Damage & Repair(tgid=10) ⓘ

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

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 4,   CDK4↓, 4,   CHK1↓, 1,   Chk2↓, 1,   cycD1/CCND1↓, 8,   CycD3↓, 1,   cycE/CCNE↓, 3,   P21↑, 5,   p27/CDKN1B↓, 1,   p27/CDKN1B↑, 3,   TumCCA↓, 1,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

HMGCR↓, 1,   IGF-1↓, 1,   p‑Jun↓, 1,   TumCG↓, 1,   TumCP↓, 4,   Wnt↓, 2,  

Migration(tgid=13) ⓘ

E-cadherin↑, 1,   EMT↓, 1,   FAK↓, 1,   ITGA5↓, 1,   ITGB1↓, 1,   MMP2↓, 3,   MMP7↓, 2,   MMP9↓, 6,   MMPs↓, 1,   PDGF↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCA↓, 1,   TumCI↓, 4,   TumCMig↓, 2,   TumMeta↓, 1,   TumMeta↑, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 2,   Hif1a↓, 1,   NO↓, 1,   VEGF↓, 2,  

Barriers & Transport(tgid=15) ⓘ

MMP↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 5,   IL1↑, 1,   IL10↑, 1,   IL1β↓, 1,   IL2↑, 1,   IL4↑, 2,   IL6↓, 3,   Inflam↓, 2,   NF-kB↓, 13,   NF-kB↑, 1,   NF-kB↝, 1,   p65↓, 1,   PGE2↓, 5,   PSA↓, 1,   PSA∅, 1,   TNF-α↓, 3,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

GR↑, 1,   PPARγ↓, 1,   PPARγ↑, 3,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 3,   Dose↝, 2,   GSTA1↑, 1,   selectivity↑, 1,   Synergy↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   IL6↓, 3,   PSA↓, 1,   PSA∅, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3,   cardioP↑, 1,   OS↑, 1,   QoL↑, 1,  
Total Targets: 144

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 13,   ARE↑, 1,   Catalase↑, 7,   GPx↑, 3,   GSH↑, 5,   GSR↑, 1,   GSTs↓, 1,   GSTs↑, 2,   H2O2↓, 1,   HO-1↑, 4,   lipid-P↓, 3,   MDA↓, 5,   MPO↓, 1,   NOX4↓, 2,   NQO1↑, 1,   Nrf1↑, 1,   NRF2↑, 7,   ROS↓, 10,   SOD↑, 7,   TAC↑, 2,   Trx1↑, 1,   VitC↑, 1,   VitE↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mtDam↓, 2,   OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACC↓, 1,   ALAT↓, 2,   CRM↑, 1,   FASN↓, 1,   LDL↓, 1,   SIRT1↑, 1,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   iNOS↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 1,   Akt↑, 1,   ERK↓, 1,   JNK↓, 2,   MAPK↓, 1,   PI3K↑, 1,   STAT3↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

Ki-67↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Ki-67↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,   Ca+2↓, 1,   Ca+2↝, 1,   LRP1↑, 1,   MMP2↑, 1,   MMPs↓, 1,   MUC1↑, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TGF-β1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 3,   VCAM-1↓, 1,   VEGF↑, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   IBI↑, 1,   MMP↓, 1,   MMP↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 6,   ICAM-1↓, 2,   IL1↓, 4,   IL10↑, 2,   IL12↓, 1,   IL1β↓, 4,   IL22↓, 1,   IL6↓, 7,   IL8↓, 3,   IL8↑, 1,   Inflam↓, 9,   NeuroI↓, 1,   NF-kB↓, 12,   p65↓, 1,   RAGE↓, 2,   TLR2↓, 1,   TLR4↓, 1,   TNF-α↓, 6,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,   ADAM10↑, 1,   BDNF↑, 4,   MAOA↓, 1,   NGF↑, 1,  

Protein Aggregation(tgid=19) ⓘ

APP↓, 1,   Aβ↓, 1,   Aβ42↓, 1,   BACE/β-secretase↓, 1,   tau↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 5,   BioAv↝, 3,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 2,   Half-Life↑, 1,   P450↑, 1,   Synergy↑, 5,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2,   AST↓, 2,   BMD↑, 1,   BP↓, 2,   creat↓, 1,   IL6↓, 7,   LDH↓, 1,   RAGE↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiArt↑, 1,   AntiCan↑, 2,   AntiMyl↑, 1,   cardioP↑, 8,   cognitive↑, 4,   hepatoP↑, 2,   Learn↑, 1,   memory↑, 5,   neuroP↑, 10,   Obesity↓, 1,   radioP↑, 1,   RenoP↑, 2,   Risk↓, 1,   toxicity∅, 1,   Wound Healing↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 125

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
25 Lycopene
1 Quercetin
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#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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