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| Artemisinin a compound in a Chinese herb that may inhibit tumor growth and metastasis
Artemisinin (antimalarial drugs) Artesunic acid (Artesunate) , Dihydroartemisinin (DHA), artesunate, arteether, and artemether, SM735, SM905, SM933, SM934, and SM1044 The induction of OS in tumor cells via the production of ROS is the key mechanism of ART against cancer. combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells. Summary: - Pro-oxidant, mechanism related with iron (hence avoid supplements containing iron? Or perhaps take with iron?) -ROS seems to affect both cancer and normal cells - Delivery of artemisinin in conjugate form with transferrin or holotransferrin (serum iron transport proteins) have been shown to greatly improve its effectiveness. - Potential direct inhibitor of STAT3 - Artemisinin synergized with the glycolysis inhibitor 2DG (2-deoxy- D -glucose) ART Combined Therapy: Allicin, Resveratrol, Curcumin, VitC (but not orally at same time), Butyrate , 2-DG, Aminolevulinic AcidG -possible problems with liver toxicity?? -Artesunate (ART), an artemisinin compound, is known for lysosomal degradation of ferritin, inducing oxidative stress and promoting cancer cell death. Pathways: - Increasing reactive oxygen species (ROS) production. This oxidative stress can cause the loss of mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspase cascades. - Downregulate HIF-1α - By impairing glycolysis, artemisinin might force cells to rely on oxidative phosphorylation (OXPHOS) for energy production. - Inhibit GLUT1 (glucose uptake), HK2, PKM2 (slow the glycolytic flux, thereby reducing the energy supply) -Artemisinin has a half-life of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hour. BioAv 21%, poor-good solubility. Artesunate (ART), a water soluble derivative of artemisinin. concentrations higher in blood, colon, liver, kidney (highly perfused organs) Pathways: - induce ROS production, iron dependent (affect both cancer and normal cells) - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, - Both Lowers (and raises) AntiOxidant defense in Cancer Cells: NRF2↓(contary), SOD↓, GSH↓ Catalase↓ GPx↓ - Small evidence of Raising AntiOxidant defense in Normal Cells: ROS↓(contary), NRF2↑, SOD↑(contary), GSH↑, Catalase↑">Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, NF-κB↓, TGF-β↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TOP1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, ECAR↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓, - some small indication of inhibiting Cancer Stem Cells : CSC↓, Hh↓, β-catenin↓, sox2↓, OCT4↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - Synergies: chemo-sensitization, RadioSensitizer, Others(review target notes), - Selectivity: Cancer Cells vs Normal Cells |
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| Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases. Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer. Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Catalase and Cancer Oxidative Stress and Cancer: Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis. Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells. Expression Levels in Different Cancers: Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior. Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis. Prognostic Implications: Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress. Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched). |
| 3386- | ART/DHA, | Effects of Caffeine-Artemisinin Combination on Liver Function and Oxidative Stress in Selected Organs in 7,12-Dimethylbenzanthracene-Treated Rats |
| - | in-vivo, | Nor, | NA |
| 3385- | ART/DHA, | Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study |
| - | Study, | NA, | NA |
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