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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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| SP2 (Specificity Protein 2) and SP3 (Specificity Protein 3) are also members of the Sp/KLF (Sp1/Krüppel-like factor) family of transcription factors, similar to SP1. They share some functional similarities but also have distinct roles in cellular processes and cancer biology. -Sp proteins are a family of transcription factors that play a crucial role in regulating gene expression. -SP1 is often overexpressed in various types of cancer, including breast, prostate, and lung cancers. However, expression levels of Sp in normal cells and tissues are low to undetectable. SP inhibitors: -Curcumin, Resveratrol, EGCG, Genistein, Piperlongumine, Betulinic acid |
| 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 |
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