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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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AMPK: guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways. -Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation. AMPK activators: -metformin or AICAR -Resveratrol: activate AMPK indirectly -Berberine -Quercetin: may stimulate AMPK -EGCG: thought to activate AMPK -Curcumin: may activate AMPK -Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models. -Alpha-Lipoic Acid (ALA): associated with AMPK activation |
3265- | Lyco,  |   | Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway |
- | in-vitro, | Nor, | NA |
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