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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↓, 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 |
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uPA (urokinase plasminogen activator) is a serine protease that plays a crucial role in the conversion of plasminogen to plasmin, an enzyme responsible for degrading various components of the extracellular matrix (ECM). This activity is central to processes such as tissue remodeling, cell migration, and angiogenesis. In the context of cancer, uPA facilitates tumor invasion and metastasis by promoting ECM degradation, while its interaction with its receptor (uPAR) and inhibitors (such as PAI-1) forms a regulatory axis that is frequently dysregulated in malignancies. Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS. Elevated uPA expression has been observed in a broad range of cancers, including breast, colorectal, lung, and prostate cancers. These high levels are often indicative of increased proteolytic activity within the tumor microenvironment. Tumors with aggressive behavior often exhibit upregulation of uPA, along with its receptor uPAR. This upregulation enhances plasmin generation and leads to an environment conducive to invasion and metastasis. Elevated uPA levels in tumor tissues have been strongly associated with poor clinical outcomes. High uPA expression is correlated with increased risk of metastasis, higher likelihood of recurrence, and reduced overall survival in several cancer types. |
3267- | Lyco,  |   | Lycopene inhibits angiogenesis both in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways |
- | in-vitro, | Nor, | HUVECs |
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