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| Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes. -Note half-life 3-4hrs - Oral BioAv low (40-50%) Pathways: - induce ROS production in cancer cells, but also known to reduce it. Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ - Does not appear to lower antioxidants in cancer cells - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓, - inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑, - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, - inhibits Cancer Stem Cells : CD133↓, β-catenin↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells |
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| LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits. LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels. However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism. Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis. Inhibitors: Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors. • Galloflavin: A flavonoid compound found in the plant Galphimia gracilis, which has been shown to inhibit LDH and have anti-cancer activity. • Fisetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Quercetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Kaempferol: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Resveratrol: A polyphenol compound found in grapes and other plants, which has been shown to inhibit LDH and have anti-cancer activity. • Curcumin: A polyphenol compound found in turmeric, which has been shown to inhibit LDH and have anti-cancer activity. • Berberine: A compound found in the plant Berberis, which has been shown to inhibit LDH and have anti-cancer activity. • Honokiol: A lignan compound found in the plant Magnolia, which has been shown to inhibit LDH and have anti-cancer activity. • Silibinin: A flavonoid compound found in milk thistle, which has been shown to inhibit LDH and have anti-cancer activity. Others:Ursolic acid, Oleanolic acid, Limonin, Allicin (garlic), Taurine |
| 2841- | FIS, | Fisetin, an Anti-Inflammatory Agent, Overcomes Radioresistance by Activating the PERK-ATF4-CHOP Axis in Liver Cancer |
| - | in-vitro, | Nor, | RAW264.7 | - | in-vitro, | Liver, | HepG2 | - | in-vitro, | Liver, | Hep3B | - | in-vitro, | Liver, | HUH7 |
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