| 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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| Protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress. The endoplasmic reticulum (ER) stress signaling pathway plays a crucial role in maintaining cellular homeostasis and responding to various stressors, including those encountered in cancer. When cells experience stress, such as the accumulation of misfolded proteins, they activate a series of signaling pathways collectively known as the unfolded protein response (UPR). The UPR aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if the stress is unresolved, triggering apoptosis. The activation of ER stress pathways can contribute to resistance against chemotherapy and targeted therapies. Cancer cells may utilize the UPR to survive treatment-induced stress, making it challenging to achieve effective therapeutic outcomes. -ER stress-associated proteins include: phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12 |
| 3066- | RES, | Resveratrol triggers ER stress-mediated apoptosis by disrupting N-linked glycosylation of proteins in ovarian cancer cells |
| 3065- | RES, | Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response |
| - | in-vitro, | lymphoma, | NA |
| 3054- | RES, | Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line |
| - | in-vitro, | Melanoma, | A375 |
| 2332- | RES, | Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism |
| - | Review, | Var, | NA |
| 2330- | RES, | Resveratrol Induces Cancer Cell Apoptosis through MiR-326/PKM2-Mediated ER Stress and Mitochondrial Fission |
| - | in-vitro, | CRC, | DLD1 | - | in-vitro, | Cerv, | HeLa | - | in-vitro, | BC, | MCF-7 |
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