Lycopene / cycD1/CCND1 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)
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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.


cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
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

4797- Lyco,    A mechanistic updated overview on lycopene as potential anticancer agent
- Review, Var, NA
AntiCan↑, The anticancer potential of lycopene has been described by various in vitro cells, animal studies, and some clinical trials.
antiOx↓, anticancer potential of lycopene is mainly due to its powerful singlet-oxygen quencher characteristics, simulation of detoxifying/antioxidant enzymes production,
Apoptosis↑, initiation of apoptosis, inhibition of cell proliferation and cell cycle progression as well as modulations of gap junctional communication, the growth factors, and signal transduction pathways
TumCP↓,
TumCCA↑,
Risk↓, The link between increased lycopene consumption and reducedoccurrence of a variety of cancers has been documented by in vitro cells,animal studies, and some clinical studies.
ROS↓, The antioxidant action of lycopene toward ROS
SOD↑, Lycopene can simulate detoxifying/antioxidant enzyme productionsuch as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione reductase.
Catalase↑, . By stimulating ARE system, the lycopene can increase detoxifying/antioxidant enzymes production such as SOD, CAT, GST
GSTs↑,
ARE↑, The upregulating of the ARE system by lycopere has been studied in human BEAS-2B, HepG2, and MCF7
NRF2↑, figure 1
cycD1/CCND1↓, figure 2
cycE/CCNE↑,
CDK2↑,
p27/CDKN1B↑,
BAX↑,
Bcl-2↓,
P53↑,
ChemoSen↑, Lycopene has also been declared to have a synergistic effect with drugs used in cancer treatment [16,17,27,32]. Lycopene may contribute to improved anticancer effects of enzalutamide

4795- Lyco,    Updates on the Anticancer Profile of Lycopene and its Probable Mechanism against Breast and Gynecological Cancer
- Review, BC, 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

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

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

4778- Lyco,    Lycopene exerts cytotoxic effects by mitochondrial reactive oxygen species–induced apoptosis in glioblastoma multiforme
- in-vitro, GBM, GBM8401
BBB↑, lycopene penetration across the blood-brain barrier and its induction of apoptosis, inhibiting proliferation in GBM8401 and T98G GBM cells
Apoptosis↑,
TumCP↑,
P53↑, lycopene promoted p53 upregulation and suppressed cyclins B and cyclin D, leading to cell cycle arrest through ROS-activated ERK pathways.
CycB/CCNB1↓,
cycD1/CCND1↓,
TumCCA↓,
mt-ROS↑, Lycopene induced Mito-ROS accumulation in GBM cells
TumCG↓, Lycopene inhibits the cell growth of GBM cells

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↑,

1013- Lyco,    Lycopene induces apoptosis by inhibiting nuclear translocation of β-catenin in gastric cancer cells
- in-vitro, GC, AGS
Apoptosis↑,
DNAdam↑,
Bax:Bcl2↑,
ROS↓, AGS cells. The results showed that lycopene reduces the levels of ROS
β-catenin/ZEB1↓,
p‑GSK‐3β↓,
APC↑,
β-TRCP↑,
cMyc↓,
cycD1/CCND1↓,

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

3276- Lyco,    Lycopene modulates cellular proliferation, glycolysis and hepatic ultrastructure during hepatocellular carcinoma
- in-vivo, HCC, NA
G6PD↓, Moreover, NDEA treatment caused a significant increase in liver G6PD activity in the NDEA group when compared to the control and LycT groups.
PCNA↓, The LycT + NDEA group showed a significant decrease in mRNA expression of PCNA and Cyclin D1 when compared to the NDEA group
cycD1/CCND1↓,
P21↑, A significant increase in the expression of p21 was observed in the LycT + NDEA group when compared to the contro
Hif1a↓, Pre-treatment with LycT in NDEA-challenged mice resulted in a significant reduction in the expression of HIF-1α at week 24 when compared to the NDEA group
Glycolysis↓, Moreover, significant reductions in the activities of glycolytic enzymes following LycT pre-treatment in NDEA-challenged mice were inversely related to HCC development.

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)


Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,   antiOx↑, 1,   ARE↑, 1,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 2,   GSR↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   NRF2↓, 1,   NRF2↑, 2,   NRF2↝, 1,   ROS↓, 6,   ROS↑, 1,   mt-ROS↑, 1,   SOD↑, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

CholSyn↓, 1,   G6PD↓, 1,   Glycolysis↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   LDL↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 9,   BAX↓, 1,   BAX↑, 3,   BAX↝, 1,   Bax:Bcl2↑, 3,   Bcl-2↓, 3,   Bcl-2↑, 1,   Casp3↑, 1,   Cyt‑c↑, 1,   β-TRCP↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 4,   p‑Akt↓, 2,   Akt2↓, 1,   ERK↓, 2,   ERK↑, 1,   JAK1↓, 1,   mTOR↓, 3,   PI3K↓, 1,   RAS↓, 1,   STAT3↓, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 3,   tumCV?, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 2,   DNAdam↑, 2,   P53↓, 2,   P53↑, 5,   P53↝, 1,   cl‑PARP↑, 2,   PCNA↓, 2,   γH2AX↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 2,   CHK1↓, 1,   Chk2↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 13,   CycD3↓, 1,   cycE/CCNE↓, 3,   cycE/CCNE↑, 1,   P21↓, 1,   P21↑, 5,   p27/CDKN1B↓, 1,   p27/CDKN1B↑, 3,   TumCCA↓, 2,   TumCCA↑, 7,  

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

HMGCR↓, 1,   p‑Jun↓, 1,   TumCG↓, 2,   TumCP↓, 5,   TumCP↑, 1,   Wnt↓, 2,  

Migration(tgid=13) ⓘ

APC↑, 1,   EMT↓, 1,   FAK↓, 1,   ITGA5↓, 1,   ITGB1↓, 1,   MMP2↓, 2,   MMP9↓, 3,   MMPs↓, 1,   PDGF↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumMeta↓, 1,   TumMeta↑, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   MMP↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL1↑, 1,   IL2↑, 1,   IL4↑, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 7,   p65↓, 1,   PGE2↓, 1,   PSA↓, 1,   TNF-α↓, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARγ↓, 1,   PPARγ↑, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,   PSA↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2,   Risk↓, 2,  
Total Targets: 118

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 4,   Catalase↑, 2,   GSH↑, 1,   GSTs↑, 1,   HO-1↑, 1,   MDA↓, 2,   Nrf1↑, 1,   NRF2↑, 2,   ROS↓, 1,   SOD↑, 1,   Trx1↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,  

Cell Death(tgid=5) ⓘ

Bcl-2↑, 1,   Casp3↓, 1,   iNOS↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

JNK↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↝, 1,   LRP1↑, 1,   MUC1↑, 1,   TGF-β↓, 1,  

Barriers & Transport(tgid=15) ⓘ

IBI↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL1↓, 2,   IL10↑, 1,   IL6↓, 2,   IL8↓, 2,   Inflam↓, 2,   NeuroI↓, 1,   NF-kB↓, 3,   RAGE↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

BDNF↑, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   Synergy↑, 3,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BMD↑, 1,   IL6↓, 2,   LDH↓, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiArt↑, 1,   AntiCan↑, 1,   cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 3,   Obesity↓, 1,   RenoP↑, 1,   Risk↓, 1,   Wound Healing↑, 1,  
Total Targets: 53

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
13 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#:73  State#:%  Dir#:%
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