Database Query Results : Lycopene, , MMP9

Lyco, Lycopene: Click to Expand ⟱

Features:

Lycopene is a naturally occurring carotenoid found predominantly in tomatoes and other red fruits and vegetables.

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

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

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

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

-Note half-life 16–20 days.
BioAv Heat processing, especially when combined with a small amount of fat, significantly enhances lycopene’s bioaccessibility and absorption. (20% under optimal conditions)
Pathways:
- ROS usually goes down, but may go up or down depending on dose and environment. Lycopene may also be modified to be a "oxdiative product" which may change the behaviour.
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : EMT↓, MMPs↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : EZH2↓, P53↑, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

MMP9, MMP9: Click to Expand ⟱

Source: HalifaxProj(suppress)

Type:

Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.

Scientific Papers found: Click to Expand⟱

4782-

Lyco,

New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene

Review,

Var,

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

4784-

Lyco,

Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives

Review,

Diabetic,

Review,

CardioV,

*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↓,
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

4795-

Lyco,

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

Review,

BC,

TumCG↓, Experimental studies suggest that lycopene can inhibit tumor growth by regulating various signaling pathways for cell growth, arresting the cell cycle, and inducing cell apoptosis.
TumCCA↑,
Apoptosis↑,
P53↝, Lycopene is reported to combat breast cancer specifically via mechanisms, such as regulation of expression of p53 and Bax, suppression of cyclin D
BAX↝,
cycD1↓,
ERK↓, inhibiting the activation of ERK and Akt signaling pathway,
Akt↓,
STAT3↓, and gynecological cancer via various signaling pathways such as STAT3, Nrf2, and NF-κB, down-regulation of ITGB1, ITGA5, FAK, MMP9, and EMT markers, etc.
NRF2↝,
NF-kB↓,
ITGB1↓,
ITGA5↓,
FAK↓,
MMP9↓,
EMT↓,

4792-

Lyco,

A Comprehensive Review on the Molecular Mechanism of Lycopene in Cancer Therapy

Review,

Var,

*AntiCan↑, The antioxidant profile of lycopene promotes anticancerous properties that reduce cancer prevalence by activating cell signaling pathways and gene expression (involved in cancer cell proliferation).
*antiOx↑,
Inflam↓, Lycopene's anti-inflammatory properties suppresses the tumor growth and development- promoting pathways, such as the PI3K/Akt/mTOR pathway.
Wnt↓, anticancer property of lycopene is also evidenced by its inhibi- tory potential of the Wnt/β-catenin signaling pathway that is involved in cancer cell modulation and propagation.
β-catenin/ZEB1↓,
*ROS↓, Lycopene also suppresses and neutralizes oxidative stress and reactive oxygen species (ROS)-induced DNA damage, preventing gene mutation.
BioAv↑, high-pressure homogenization having 80 MPa pressure and 25°C temperature (Carpentieri et al. 2023),and freeze-dried tomatoes (Tan et al. 2021) have improved the bioavailability and bioaccessibility of lycopene.
ROS↓, ycopene against pancreatic acinar cells was determined, it was found that IL- 6 and NF-kB are suppressed by lycopene (2 or 5 μmol/L) after 2 h of cerulein activation, demonstrating their role in neutralizing ROS
Risk↓, Mia et al. (2023) determined prostate cancer-lowering properties of lycopene among 47,365 individuals.
PGE2↓, Lycopene also exhibited its suppressive effect by reducing PGE2, COX-2, and phosphorylated ERK1/2 protein (Marino et al. 2023).
COX2↓,
p‑ERK↓,
P21↑, lycopene and fish oil supplementation was revealed by the elevated expression of cell cycle inhibitors (p21 CIP1/WAF1 and p27Kip1) as well as by the reduced expression of MMP-7, MMP-9, COX-2, PGE2
MMP7↓,
MMP9↓,
ChemoSen↑, It was observed that lycopene and cisplatin act synergistically to arrest cell growth by enhancing Bax & Nrf2 expression and inactivating Bcl-2 and NF-kB pathways
eff↑, lycopene silver nanoparticles (LyAgNP) suppressed the progression of HeLa cells and COLO320DM cells

4788-

Lyco,

Lycopene as a potential anticancer agent: Current evidence on synergism, drug delivery systems and epidemiology (Review)

Review,

Var,

AntiCan↑, It may be associated with a reduction in the morbidity and mortality of several types of cancer, making it a prom‑ ising anticancer agent
ChemoSen↑, present review summarizes the synergistic effects of lycopene as a dietary supplement with other chemotherapy drugs or nutrients, for the enhancement of anticancer effects or the reduction of side effects from chemotherapy drugs.
chemoP↑,
Dose↝, Shao and Hathcock (20) proposed a 75 mg/day intake as the upper limit of lycopene for supplements, as no adverse effects were reported from continuous administration of 75 mg/day lycopene in a 4‑week clinical study
BioAv↑, Thermal processing of tomato products can cause changes in the structure of lycopene to shift and yield cis‑isomers in the product and this form is more bioavailable
BioAv↑, The presence of fat in food also helps enhance the absorption of lycopene (40) and its absorption is influenced by the amount of ingested fat, and the type and emulsification of dietary fat
BioAv↓, avoid the consumption of lycopene concurrently with high dietary fiber, as several types of dietary fiber (e.g. pectin, guar, alginate, etc.) are associated with lower bioavailability of lycopene
cardioP↑, figure 2
AntiDiabetic↑,
hepatoP↑,
neuroP↑,
MAPK↓, 2 mg/kg; 5 mg/kg Inhibition of MAPK signaling pathway (48) and decreased MMP‑2 and MMP‑9 activities through the activation of NM23‑H1, TIMP‑1 and TIMP‑2 expression.
MMP2↓,
MMP9↓,
TIMP1↑,
TIMP2↑,

1714-

Lyco,

Lycopene reduces ovarian tumor growth and intraperitoneal metastatic load

in-vitro,

Ovarian,

OV-MZ-6

in-vivo,

NA,

mice

ChemoSen↑, Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin
CA125↓, Lycopene decreased the expression of the ovarian cancer biomarker, CA125.
ITGA5↓, down-regulated expression of ITGA5, ITGB1, MMP9, FAK, ILK and EMT markers, decreased protein expression of integrin α5 and reduced activation of MAPK.
ITGB1↓,
MMP9↓,
FAK↓,
EMT↓,
MAPK↓,
MMP9↓, Levels of MMP9 in serum and ascites were reduced upon lycopene prevention
antiOx↑, The antioxidant properties of lycopene have been reported for the prevention and treatment of different tumor entities, especially in prostate cancer
Ki-67↓, expression of Ki67 in tumor tissues was lowered upon lycopene treatment compared to the placebo
MAPK↓, reduced the protein expression of integrin α5 and activation of MAPK signaling

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↓,

1708-

Lyco,

The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies

Review,

Var,

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

3277-

Lyco,

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

Review,

Var,

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

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,1, angioG↓,1, AntiCan↑,4, AntiDiabetic↑,1, antiOx↑,2, Apoptosis↑,2, BAX↓,1, BAX↝,1, Bax:Bcl2↑,1, Bcl-2↓,1, Bcl-2↑,1, BioAv↓,3, BioAv↑,4, BioAv↝,1, CA125↓,1, cardioP↑,1, Casp3↑,3, Catalase↑,2, CDK2↓,1, CDK4↓,1, chemoP↑,1, ChemoSen↑,5, CHK1↓,1, Chk2↓,1, cMyc↓,1, COX2↓,4, cycD1↓,3, cycE↓,1, DNAdam↓,1, Dose↝,3, E-cadherin↑,1, eff↑,2, EMT↓,2, ERK↓,2, p‑ERK↓,1, FAK↓,2, FOXO3↓,1, GPx↑,4, GR↑,1, GSH↑,2, GSR↑,1, GSTA1↑,1, hepatoP↑,1, Hif1a↓,1, HO-1↑,1, IGF-1↓,1, IGF-1R↓,1, IL1↑,1, IL10↑,1, IL2↑,1, IL4↑,2, IL6↓,2, Inflam↓,2, iNOS↓,1, ITGA5↓,2, ITGB1↓,2, JAK1↓,1, Ki-67↓,1, MAPK↓,3, MDA↓,1, MMP2↓,4, MMP7↓,3, MMP9↓,10, neuroP↑,1, NF-kB↓,6, NRF2↑,1, NRF2↝,1, OS↑,1, P21↑,3, p27↑,1, P53↓,1, P53↝,1, p65↓,1, cl‑PARP↑,1, PCNA↓,2, PGE2↓,3, PPARγ↑,2, PSA∅,1, QoL↑,1, Risk↓,1, ROS↓,3, ROS↑,1, i-ROS↓,1, SIRT1↑,1, SOD↑,2, Sp1/3/4↓,1, STAT3↓,3, survivin↓,1, TIMP1↑,2, TIMP2↑,2, TNF-α↓,2, TNF-α↑,1, TumCA↓,1, TumCCA↑,2, TumCG↓,1, TumCI↓,2, TumCMig↓,1, TumCP↓,2, TumMeta↑,1, VEGF↓,2, Wnt↓,2, β-catenin/ZEB1↓,2, γH2AX↓,1,
Total Targets: 103

Results for Effect on Normal Cells:
AntiCan↑,1, antiOx↑,3, BDNF↑,1, cardioP↑,1, IL1↓,2, IL12↓,1, IL1β↓,1, IL6↓,2, IL8↓,1, neuroP↑,1, NF-kB↓,1, Nrf1↑,1, radioP↑,1, ROS↓,1, TNF-α↓,1,
Total Targets: 15

Scientific Paper Hit Count for: MMP9, MMP9

9 Lycopene

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:203  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Lycopene, , MMP9

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