Lycopene / Akt 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↓, 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.


Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
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, MCF7 - 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/CCND1↓,
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

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

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↑,

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

3267- Lyco,    Lycopene inhibits angiogenesis both in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways
- in-vitro, Nor, HUVECs
*VEGF↓, highest dose used (400 μg/plug) completely inhibited the formation of vascular endothelial cells induced by vascular endothelial growth factor (VEGF).
*MMP2↓, lycopene inhibited tube formation, invasion, and migration in HUVECs, and such actions were accompanied by reduced activities of matrix metalloproteinase-2, urokinase-type plasminogen activator, and protein expression of Rac1
*uPA↓,
*Rac1↑,
*TIMP2↑, and by enhancing protein expression of tissue inhibitors of metalloproteinase-2 and plasminogen activator inhibitor-1.
*p38↓, lycopene attenuated VEGF receptor-2 (VEGFR2)-mediated phosphorylation of extracellular signal-regulated kinase (ERK), p38, and Akt as well as protein expression of PI3K.
*Akt↓,
*angioG↓, anti-angiogenic effect of lycopene both in vitro and in vivo.

1126- Lyco,    Lycopene Inhibits Epithelial–Mesenchymal Transition and Promotes Apoptosis in Oral Cancer via PI3K/AKT/m-TOR Signal Pathway
- vitro+vivo, Oral, NA
TumCP↓,
TumCMig↓,
TumCI↓,
Apoptosis↑,
EMT↓,
PI3K↓,
Akt↓,
mTOR↓,
E-cadherin↓,
BAX↑,
N-cadherin↓,
p‑PI3K↓,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,

3828- Lyco,    Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease
- in-vitro, AD, M146L
*ROS↓, Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins.
*PI3K↑,
*Akt↑,
*NRF2↓,
*antiOx↑,
*BACE/β-secretase↓, lycopene inhibited β -secretase (BACE) activity in M146L cells.
*MDA↓,

3532- Lyco,    Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer’s disease
- in-vitro, AD, NA
*ROS↓, Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins.
*PI3K↑,
*Akt↑,
*NRF2↑,
*antiOx↑,
*Aβ↓, Lycopene possibly prevents Aβ-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells.
*Apoptosis↓, Lycopene alleviates apoptosis in M146L cells
*neuroP↑, lycopene shows the neuroprotective effects of antioxidative damage and antiapoptotic by reducing the phosphorylation of PI3K/Akt

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

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)

3274- Lyco,    Lycopene enhances the sensitivity of castration-resistant prostate cancer to enzalutamide through the AKT/EZH2/ androgen receptor signaling pathway
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B
Akt↓, enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway,
EZH2↓,


Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↑, 1,   Keap1↝, 1,   lipid-P↓, 1,   NRF2↑, 1,   NRF2↝, 2,   ROS↓, 3,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

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

Cell Death(tgid=5) ⓘ

Apoptosis↑, 5,   BAX↑, 3,   BAX↝, 1,   Bax:Bcl2↑, 2,   Bcl-2↓, 2,   Cyt‑c↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 6,   Akt↝, 1,   p‑Akt↓, 3,   ERK↓, 1,   ERK↑, 1,   mTOR↓, 4,   mTOR↝, 1,   p‑mTOR↓, 1,   PI3K↓, 2,   PI3K↝, 1,   p‑PI3K↓, 1,   RAS↓, 1,   STAT3↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 1,   EZH2↓, 1,   tumCV?, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 3,   P53↝, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycD1/CCND1↓, 6,   CycD3↓, 1,   cycE/CCNE↓, 2,   P21↓, 1,   P21↑, 3,   p27/CDKN1B↓, 1,   p27/CDKN1B↑, 2,   TumCCA↓, 1,   TumCCA↑, 5,  

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

HMGCR↓, 1,   p‑Jun↓, 1,   TumCG↓, 1,   TumCP↓, 3,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

E-cadherin↓, 1,   EMT↓, 2,   FAK↓, 1,   ITGA5↓, 1,   ITGB1↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   PDGF↓, 1,   TumCI↓, 3,   TumCMig↓, 2,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  

Barriers & Transport(tgid=15) ⓘ

MMP↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

NF-kB↓, 4,   NF-kB↝, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARγ↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   selectivity↑, 1,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EZH2↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   Risk↓, 1,  
Total Targets: 75

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 6,   Catalase↑, 3,   GPx↑, 1,   GSH↑, 3,   GSR↑, 1,   GSTs↓, 1,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   MDA↓, 3,   MPO↓, 1,   NRF2↓, 1,   NRF2↑, 4,   ROS↓, 5,   SOD↑, 3,   TAC↑, 1,   Trx1↑, 1,   VitC↑, 1,   VitE↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   iNOS↓, 1,   p38↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 2,   Akt↑, 3,   MAPK↓, 1,   PI3K↑, 3,  

Migration(tgid=13) ⓘ

LRP1↑, 1,   MMP2↓, 1,   MUC1↑, 1,   Rac1↑, 1,   TGF-β↓, 1,   TGF-β1↑, 1,   TIMP2↑, 1,   uPA↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   NO↓, 1,   VEGF↓, 1,   VEGF↑, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   IBI↑, 1,   MMP↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2,   IL10↑, 2,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 3,   NeuroI↓, 1,   NF-kB↓, 3,   RAGE↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

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

Protein Aggregation(tgid=19) ⓘ

APP↓, 1,   Aβ↓, 2,   Aβ42↓, 1,   BACE/β-secretase↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BMD↑, 1,   IL6↓, 1,   LDH↓, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiArt↑, 1,   AntiMyl↑, 1,   cardioP↑, 2,   cognitive↑, 2,   hepatoP↑, 1,   Learn↑, 1,   memory↑, 3,   neuroP↑, 5,   Obesity↓, 1,   RenoP↑, 1,   Risk↓, 1,   Wound Healing↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 88

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
14 Lycopene
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:4  State#:%  Dir#:%
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