condition found tbRes List
Lyco, Lycopene: Click to Expand ⟱
Features:
Lycopene is a naturally occurring carotenoid found predominantly in tomatoes and other red fruits and vegetables.

Antioxidant Properties:
-Lycopene is a powerful antioxidant. It helps neutralize free radicals, which can reduce oxidative stress—a factor implicated in cancer development. Possible concern about interfering with chemotherapy and radiation therapy. However this review disagrees.
Inflammation Reduction:
-Some studies suggest that lycopene may help lower levels of inflammation, another process linked to cancer progression

At supraphysiological or extremely high concentrations, lycopene may have the potential to switch from an antioxidant to a prooxidant role
-The prooxidant effect of lycopene has been observed under conditions of high oxygen tension. In vitro studies have suggested that in environments with elevated oxygen levels, lycopene might promote rather than neutralize the production of reactive oxygen species (ROS).
-The presence of metal ions (such as iron or copper) in the environment can catalyze reactions where antioxidants, including lycopene, contribute to oxidative processes. These metals can interact with lycopene, potentially leading to the formation of radicals.

The mevalonate pathway produces cholesterol and a variety of isoprenoids, which are important for maintaining cell membrane integrity, protein prenylation, and other essential cellular functions.
-One of the primary enzymes in this pathway is HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase), which is the target of statin drugs used for lowering cholesterol. Some studies suggest that lycopene might downregulate the activity of HMG-CoA reductase or other enzymes in the mevalonate pathway. By doing so, lycopene could potentially reduce the synthesis of cholesterol and isoprenoids that are necessary for rapid cell proliferation—an especially relevant aspect in cancer cells.

Lycopene typically used in a 100mg/day range for cancer (inhibition of the the Melavonate Pathway)
-also has antiplatelet aggregation capability.

-Note half-life 16–20 days.
BioAv Heat processing, especially when combined with a small amount of fat, significantly enhances lycopene’s bioaccessibility and absorption. (20% under optimal conditions)
Pathways:
- ROS usually goes down, but may go up or down depending on dose and environment
- Raises AntiOxidant defense in Normal Cells: ROS↓">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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
1566- betaCar,  Lyco,    Antioxidant and pro-oxidant effects of lycopene in comparison with beta-carotene on oxidant-induced damage in Hs68 cells
- in-vitro, Nor, HS68
*ROS↑, beta-carotene is known to have pro-oxidant activity in vitro
*ROS⇅, The present study in Hs68 cells demonstrates that lycopene can be either an antioxidant or a pro-oxidant depending on the oxidants used, and that lycopene and beta-carotene behave similarly under the in vitro oxidative conditions.
*Dose?, Both the antioxidant and pro-oxidant effects of lycopene tended to be dose-dependent

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↓,

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↓, 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↓,

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

3277- Lyco,    Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent
- Review, Var, NA
antiOx↑, lycopene provides a strong antioxidant activity that is 100 times more effective than α-tocopherol and more than double effective that of β-carotene
TumCP↓, In vivo and in vitro experiments have demonstrated that lycopene at near physiological levels (0.5−2 μM) could inhibit cancer cell proliferation [[22], [23], [24]], induce apoptosis [[25], [26], [27]], and suppress metastasis [
Apoptosis↑,
TumMeta↑,
ChemoSen↑, lycopene can increase the effect of anti-cancer drugs (including adriamycin, cisplatin, docetaxel and paclitaxel) on cancer cell growth and reduce tumour size
BioAv↓, low water solubility and bioavailability of lycopene
Dose↝, The concentration of lycopene in plasma (daily intake of 10 mg lycopene) is approximately 0.52−0.6 μM
BioAv↓, significant decrease in lycopene bioavailability in the elderly
BioAv↑, oils and fats favours the bioavailability of lycopene [80], while large molecules such as pectin can hinder the absorption of lycopene in the small intestine due to their action on lipids and bile salt molecules
SOD↑, GC: 50−150 mg/kg BW/day ↑SOD, CAT, GPx ↑IL-2, IL-4, IL-10, TNF-α ↑IgA, IgG, IgM ↓IL-6
Catalase↑,
GPx↑,
IL2↑, lycopene treatment significantly enhanced blood IL-2, IL-4, IL-10, TNF-α levels and reduced IL-6 level in a dose-dependent manner.
IL4↑,
IL1↑,
TNF-α↑,
GSH↑, GC: ↑GSH, GPx, GST, GR
GPx↑,
GSTA1↑,
GSR↑,
PPARγ↑, ↑GPx, SOD, MDA ↑PPARγ, caspase-3 ↓NF-κB, COX-2
Casp3↑,
NF-kB↓,
COX2↓,
Bcl-2↑, AGS cells Lycopene 5 μM ↑Bcl-2 ↓Bax, Bax/Bcl-2, p53 ↓Chk1, Chk2, γ-H2AX, DNA damage ↓ROS Phase arrest
BAX↓,
P53↓,
CHK1↓,
Chk2↓,
γH2AX↓,
DNAdam↓,
ROS↓,
P21↑, CRC: ↑p21 ↓PCNA, β-catenin ↓COX-2, PGE2, ERK1/2 phosphorylated
PCNA↓,
β-catenin/ZEB1↓,
PGE2↓,
ERK↓,
cMyc↓, AGS cells: ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS
cycE↓,
JAK1↓,
STAT3↓,
SIRT1↑, Huh7: ↑SIRT1 ↓Cells growth ↑PARP cleavage ↓Cyclin D1, TNFα, IL-6, NF-κB, p65, STAT3, Akt activation ↓Tumour multiplicity, volume
cl‑PARP↑,
cycD1↓,
TNF-α↓,
IL6↓,
p65↓,
MMP2↓, SK-Hep1 human hepatoma cells Lycopene 5, 10 μM ↓MMP-2, MMP-9 ↓
MMP9↓,
Wnt↓, AGS cells Lycopene 0.5 μM, 1 μM ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS

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↓, 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

3529- Lyco,    The antioxidant and anti-inflammatory properties of lycopene in mice lungs exposed to cigarette smoke
- in-vivo, Nor, NA
*antiOx↑, Lycopene is a carotenoid with known antioxidant and anti-inflammatory properties.
*Inflam↓,
*ROS↓, Lycopene concentrations of 1 μM and 2 μM were able to reduce the production of ROS in 24 h compared with CS.
*TNF-α↓, There was an increase in the levels of tumor necrosis factor-α, interferon-γ and interleukin-10 after exposure to CS, and these effects were suppressed by both doses of lycopene.
*IFN-γ↓,
IL10↓,

3530- Lyco,    Lycopene Scavenges Cellular ROS, Modulates Autophagy and Improves Survival through 7SK snRNA Interaction in Smooth Muscle Cells
- in-vitro, Stroke, NA
*ROS↓, The reactive oxygen species (ROS) were reduced from 8 fold to 3 fold post addition of lycopene for 24 h.
*antiOx↑, Lycopene administration during ischemic heart disease might improve the functions of the smooth muscle cells and 7SK snRNA might be involved in the binding of lycopene and its antioxidant protective effects.
*TNF-α↓, Addition of Lycopene to the media showed diminished TNF-α expression (p < 0.0429) compared to the stressed group.

3531- Lyco,    Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system
- in-vivo, Nor, NA
*NRF2↑, After LYC intervened in the body, it activated Nrf2 nuclear translocation and its downstream HO-1 and NQO1 antioxidant signaling pathways
*HO-1↑, Lycopene activates Nrf2-HO-1 antioxidant pathway to inhibit oxidative stress injury induced by AAI exposure in NRK52E cells
*NQO1↑,
*ROS↓, LYC inhibited ROS production by renal tubular epithelial cells, and alleviated mitochondrial damage.
*mtDam↓,
*Bcl-2↑, LYC was able to up-regulate the expression of Bcl-2, down-regulate Bax expression and inhibit the activation of cleaved forms of Caspase-9 and Caspase-3, which finally attenuated the apoptosis
*BAX↓,
*Casp9↓,
*Casp3↓,
*Apoptosis↓,
*RenoP↑, Interestingly, there was a significant improvement in damaged renal tissue in mice with AAN after lycopene intervention
*lipid-P↓, lycopene significantly decreased the expression of AAI-induced lipid peroxidation product (MDA), and increased the expression of antioxidant enzyme systems (T-AOC, SOD, and GSH-PX)
*SOD↑,
*GPx↑,
*Inflam↓, Lycopene improves inflammatory responses in the kidneys of AAN mice
*TNF-α↓, TNF-α, IL-6, IL-10, was increased and the expression of IL-12 was decreased in the kidneys of model mice compared with the control group. However, LYC intervention reversed the expression of these genes in a dose-dependent manner
*IL6↓,
*IL10↓,

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

3533- Lyco,  Chemo,    Lycopene and chemotherapy toxicity
- Review, Var, NA
*ROS↓, Lycopene is a major carotenoid present in tomatoes, and it is a potent antioxidant that may provide protection against cellular damage caused by ROS.
*antiOx↑,
*chemoP↑, Lycopene may reduce or prevent the side effects of chemotherapy due to its antioxidant and anti-inflammatory properties.
*Inflam↓,

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↑,

1710- Lyco,    Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases
- Review, CardioV, NA
antiOx↓, Lycopene is a potent antioxidant that fights ROS and, subsequently, complications.
ROS↓,
BP↓, It reduces blood pressure via inhibiting the angiotensin-converting enzyme and regulating nitrous oxide bioavailability.
LDL↓, important role in lowering of LDL (low-density lipoproteins) and improving HDL (high-density lipoproteins) levels to minimize atherosclerosis
*toxicity∅, Lycopene is a natural substance that may be used in high doses as a dietary supplement without causing harm to human health or physiology
eff↑, Thermal food processing, particularly in the presence of cooking oils, causes lycopene to micellize and enhance its intestinal absorption rate by a factor of ten
ROS↑, As a pro-oxidant, lycopene may have both good and negative impacts in biological systems, as well as influence the course of human illnesses.
*Half-Life↑, Plasma lycopene has a half-life of 12–33 days in the human body
*BioAv↓, Tomato lycopene is not easily absorbed since it is integrated into the nutritional matrix.
*BioAv↑, Clinical research demonstrates that heat-processed tomato products absorb lycopene more quickly than raw sources, and that adding oil increases absorption
*antiOx↑, Lycopene’s ability to protect against oxidative stress has been established

1711- Lyco,    Nutritional Importance of Carotenoids and Their Effect on Liver Health: A Review
- Review, Var, NA
ROS↑, exposure to high doses of carotenoids has a pro-oxidant effect
Dose↓, lycopene, an intake of 5 to 7 mg per day was recommended for healthy people to maintain the circulating levels of this carotenoid, in order to combat oxidative stress and prevent chronic diseases
Dose↑, higher concentrations of lycopene (35–75 mg/day) may be required when there is a disease, such as cancer and cardiovascular diseases.
antiOx↑, main protective effect of lycopene is due to its antioxidant effect through the inactivation of ROS and the extinction of free radicals
P450↓, significant decrease in cytochrome P450 2E1
TNF-α↓, TNF-α, IL-1β, and IL-12) were also found
IL1β↓,
IL12↓,

1712- Lyco,    Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair
- in-vitro, Lung, A549
ROS↓, Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability
ROS↑, we found that lycopene only exerted antioxidative effects at low-dosage, while such beneficial effects were diminished at high-dosage
eff↑, suggesting an increased carotenoid uptake in the cells under oxidative stress

1713- Lyco,    Lycopene: A Potent Antioxidant with Multiple Health Benefits
- Review, Nor, NA
*antiOx↑, As one of the most potent antioxidants, its capacity to neutralise singlet oxygen is double that of ?-carotene, ten times greater than that of ?-tocopherol, and one hundred and twenty-five times more effective than glutathione
*ROS⇅, lycopene acts as an antioxidant in systems that produce singlet oxygen but behaves as a pro-oxidant in systems that create peroxide
*Dose↝, In low doses, it acts as an antioxidant, but at high doses, it acts as a pro-oxidant
*eff↑, In situation where there is an imbalance between antioxidant defences and ROS production, such as during inflammation or exposure to environmental toxins [91], lycopene may switch from its antioxidant role to a pro-oxidant role
*LDL↓, Wistar rats given a high-fat diet and 50mg/kg body weight of lycopene daily for 3mths had significant reductions in plasma total cholesterol, triglycerides, and lLDL levels but increased HDL cholesterol
*RenoP↑, shown to protect the kidney against chemically induced damage
*Inflam↓, evidence is plentiful demonstrating the anti-inflammatory effects of lycopene both in vitro and in vivo
neuroP↑, mice with Alzheimer's disease induced by ? amyloid, lycopene reduced oxidative stress, decreased neuronal loss, improved synaptic plasticity, and inhibited neuroinflammation
Rho↓, lycopene treatment was demonstrated to have the potential to mitigate vascular arteriosclerosis in allograft transplantation by inhibiting Rho-associated kinases

1715- Lyco,    Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence
- Review, Var, NA
antiOx↑, Carotenoids are well known for their potent antioxidant function in the cellular system.
ROS↑, However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis
ChemoSen↑, when carotenoids are delivered with ROS-inducing cytotoxic drugs, they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants
selectivity↑, In cancer cells with innately high intracellular ROS levels, carotenoids may act as pro-oxidants and trigger ROS-mediated apoptosis of cancer cells.
eff↓, However, under high oxygen tension conditions (e.g., in the lungs of smokers), β-carotene shows tumor-promoting effects.
Casp3↑,
Casp7↑,
Casp9↑,
P53↑,
BAX↑,
DNAdam↑,
mtDam↑, mitochondrial dysfunction
eff↑, Astaxanthin co-treatment with β-carotene and lutein (equimolar 5 µM each)

1716- Lyco,    Anti-inflammatory Activity of β-Carotene, Lycopene and Tri-n-butylborane, a Scavenger of Reactive Oxygen Species
- in-vitro, AML, RAW264.7
antiOx↑, carotenoids β-carotene and lycopene are antioxidants that not only quench singlet oxygen but also inhibit lipid peroxidation
lipid-P↓,
ROS↑, These findings could explain the intriguing pro-oxidant and cytotoxic activity of β-carotene.
Dose↑, new radical peaks then becoming slightly but reproducibly evident at concentrations over 10 mM

1717- Lyco,    Potential Role of Carotenoids as Antioxidants in Human Health and Disease
- Review, Var, NA
antiOx↑, unique antioxidative properties.
ROS⇅, The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids
ROS↑, antioxidant potential (e.g., lutein) or even leads to pro-oxidant behavior (i.e., zeaxanthin)

1718- Lyco,    The role of carotenoids in the prevention of human pathologies
- Review, Var, NA
ROS⇅, Thus, in thymocytes, β-Carotene is an antioxidant at low oxygen pressure but a pro-oxidant at high oxygen concentrations
ROS↑, lycopene may have also prooxidant activities depending on the type of oxidants used.

1719- Lyco,    Lycopene for the prevention and treatment of prostate disease.
- Review, Var, NA
ROS⇅, Lycopene, a member of the carotenoid family, found commonly in red pigmented fruit and vegetables has been established as having strong antioxidant and pro-oxidant properties.

1720- Lyco,    Antioxidant and Pro-oxidant Activities of Carotenoids
- Review, Nor, NA
ROS↑, lycopene (50 μM) exhibited pro-oxidant effects in in vitro cellular assays with several cancer cell lines (PC-3), (A549), (HeLa), (MCF-7), (A431), and (HepG2)

1721- Lyco,  RES,  VitC,    Lycopene, resveratrol, vitamin C and FeSO4 increase damage produced by pro-oxidant carcinogen 4-nitroquinoline-1-oxide in Drosophila melanogaster: Xenobiotic metabolism implications.
- in-vitro, Pca, PC3 - in-vitro, Lung, A549 - in-vitro, Cerv, HeLa - in-vitro, BC, MCF-7 - in-vitro, Liver, HepG2
ROS↑, We propose that the basal levels of the XM's enzymes in the ST cross interacted with a putative pro-oxidant activity of the compounds added to the pro-oxidant effects of 4-NQO.

3260- Lyco,    Lycopene in human health
- Review, NA, NA
*BioAv↝, Lycopene bioavailability is lower in raw sources than in thermal processed food sources.
*BioAv↓, As a result of the low bioavailability of lycopene, its circulating levels are more suitable as prognostic data for health outcomes than its dietary intake values
*ROS⇅, A beneficial or prejudicial cellular response by lycopene will depend on its antioxidant or prooxidant properties respectively, depending on the cellular and extracellular environment
*BioAv↝, Thus, there is less bioavailability of lycopene in fresh tomatoes than in processed tomato products (such as pasteurized tomato juice, soup, sauce and ketchup)

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↓, downregulation of cyclooxygenase 2,
*LDL↓, significant reductions in total and LDL cholesterol were revealed only at doses of, at least, 25 mg lycopene/day
*eff↑, 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
*eff↑, 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↓,
*RAGE↓,

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↓,

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↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   antiOx↓,1,   antiOx↑,5,   APC↑,1,   Apoptosis↑,2,   BAX↓,1,   BAX↑,1,   Bax:Bcl2↑,1,   Bcl-2↑,1,   BioAv↓,2,   BioAv↑,1,   BP↓,1,   cardioP↑,1,   Casp3↑,2,   Casp7↑,1,   Casp9↑,1,   Catalase↑,1,   CDK2↓,2,   CDK4↓,2,   ChemoSen↑,2,   CHK1↓,1,   Chk2↓,1,   cMyc↓,2,   COX2↓,1,   cycD1↓,3,   cycE↓,2,   DNAdam↓,1,   DNAdam↑,2,   Dose↓,1,   Dose↑,2,   Dose↝,1,   eff↓,1,   eff↑,3,   ERK↓,1,   GPx↑,2,   GSH↑,2,   GSK‐3β↓,1,   p‑GSK‐3β↓,1,   GSR↑,1,   GSTA1↑,1,   IGF-1R↓,1,   IL1↑,1,   IL10↓,1,   IL12↓,1,   IL1β↓,1,   IL2↑,1,   IL4↑,1,   IL6↓,1,   JAK1↓,1,   LDL↓,1,   lipid-P↓,2,   MMP2↓,1,   MMP9↓,2,   MMPs↓,1,   mtDam↑,1,   mTOR↓,1,   neuroP↑,1,   NF-kB↓,3,   NOX↓,1,   NOX4↓,1,   NRF2↑,1,   P21↑,2,   p27↓,1,   P450↓,1,   P53↓,1,   P53↑,2,   p65↓,1,   cl‑PARP↑,1,   PCNA↓,1,   PGE2↓,3,   PPARγ↑,1,   Rho↓,1,   ROS↓,7,   ROS↑,9,   ROS⇅,3,   i-ROS↓,1,   selectivity↑,1,   SIRT1↑,1,   SOD↑,1,   Sp1/3/4↓,1,   STAT3↓,2,   TNF-α↓,2,   TNF-α↑,1,   TumCCA↑,1,   TumCI↓,2,   TumCMig↓,1,   TumCP↓,1,   TumMeta↑,1,   Wnt↓,1,   β-catenin/ZEB1↓,2,   β-TRCP↑,1,   γH2AX↓,1,  
Total Targets: 92

Results for Effect on Normal Cells:
ACC↓,1,   Akt↓,1,   Akt↑,1,   ALAT↓,1,   AntiAg↑,1,   AntiCan↑,1,   antiOx↑,10,   Apoptosis↓,2,   AST↓,1,   Aβ↓,1,   BAX↓,1,   BBB↑,1,   Bcl-2↑,1,   BioAv↓,4,   BioAv↑,3,   BioAv↝,3,   BP↓,1,   Ca+2↓,1,   cardioP↑,5,   Casp3↓,1,   Casp9↓,1,   Catalase↑,3,   chemoP↑,1,   cognitive↑,1,   COX2↓,5,   creat↓,1,   DNAdam↓,1,   Dose?,1,   Dose↑,1,   Dose↝,3,   eff↑,3,   ER Stress↓,1,   ERK↓,1,   FASN↓,1,   GPx↑,2,   GSH↑,3,   GSR↑,1,   GSTs↓,1,   GSTs↑,1,   H2O2↓,1,   Half-Life↑,2,   hepatoP↑,1,   HO-1↑,4,   ICAM-1↓,2,   IFN-γ↓,1,   IL1↓,1,   IL10↓,1,   IL10↑,1,   IL1β↓,2,   IL22↓,1,   IL6↓,4,   IL8↓,1,   Inflam↓,8,   iNOS↓,2,   Ki-67↓,1,   LDL↓,2,   lipid-P↓,2,   MAPK↓,1,   MDA↓,2,   memory↑,2,   MMP2↑,1,   MMPs↓,1,   MPO↓,1,   mtDam↓,2,   neuroP↑,5,   NF-kB↓,5,   NO↓,3,   NOX4↓,2,   NQO1↑,2,   NRF2↑,5,   P450↑,1,   p65↓,1,   PI3K↑,1,   RAGE↓,1,   RenoP↑,3,   ROCK1↓,1,   ROS↓,10,   ROS↑,1,   ROS⇅,3,   SIRT1↑,1,   SOD↑,5,   SREBP1↓,1,   STAT3↓,1,   TAC↑,2,   tau↓,1,   TGF-β1↑,1,   TLR2↓,1,   TLR4↓,1,   TNF-α↓,6,   toxicity∅,2,   VCAM-1↓,1,   VitC↑,1,   VitE↑,1,  
Total Targets: 93

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
27 Lycopene
1 beta-carotene
1 Chemotherapy
1 Resveratrol
1 Vitamin C (Ascorbic Acid)
1 Quercetin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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