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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↑, - 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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| 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 |
| 3396- | ART/DHA, | Progress on the study of the anticancer effects of artesunate |
| - | Review, | Var, | NA |
| 1076- | ART/DHA, | The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer |
| - | Review, | NA, | NA |
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