| Features: polyphenol |
| Found in red grapes and products made with grapes. Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts. • Anti-inflammatory effects, Antioxidant effects: - Antiplatelet aggregation for stroke prevention - BioAvialability use piperine - some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative) -known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer. - RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs). However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM. Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects. -Note half-life 1-3 hrs?. BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine Pathways: - usually induce ROS production in cancer cells, while reducing ROS in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, - Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓ - 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 : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓, - inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - 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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| The Rho GTPases RhoA, Rac1, and Cdc42 are important regulators of cytoskeletal dynamics.
small GTPase Ras homolog gene family member A (RHOA) RHOA: Ras homolog family member A Many in vitro and in vivo data indicate tumor-promoting effects of activated Rho GTPases, also tumor suppressive functions have been described. In many cancers, RhoA and RhoC are often found to be overexpressed. RhoB expression can be downregulated in certain cancers, which may contribute to tumor progression. Unlike RhoA and RhoC, RhoB is often considered a tumor suppressor, and its loss can lead to increased cell proliferation and survival. -RhoA activity has been linked to the modulation of EMT, influencing both the disassembly of cell–cell junctions and the reorganization of the cytoskeleton necessary for migration. -Elevated levels or hyperactivation of RhoA has been associated with poor prognosis in several cancers. |
| 3083- | RES, | Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis |
| - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | BC, | MDA-MB-468 |
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