| Features: |
| 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: - One of the strongest tumor-selective pro-oxidants, mechanism related with iron. Synergizes with iron-rich tumors -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) - Minimal NRF2 activation -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 Often synergistic with ROS-based chemo |
| 2577- | ART/DHA, | Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives |
| - | Review, | Var, | NA |
| 3385- | ART/DHA, | Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study |
| - | Study, | NA, | NA |
| 3384- | ART/DHA, | Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response‑induced upregulation of CHAC1 expression |
| - | in-vitro, | Liver, | Hep3B | - | in-vitro, | Liver, | HUH7 | - | in-vitro, | Liver, | HepG2 |
| 3383- | ART/DHA, | Dihydroartemisinin: A Potential Natural Anticancer Drug |
| - | Review, | Var, | NA |
| 3382- | ART/DHA, | Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge? |
| - | Review, | Var, | NA |
| 3345- | ART/DHA, | Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells |
| - | in-vitro, | GBM, | NA |
| 2582- | ART/DHA, | 5-ALA, | Mechanistic Investigation of the Specific Anticancer Property of Artemisinin and Its Combination with Aminolevulinic Acid for Enhanced Anticolorectal Cancer Activity |
| - | in-vivo, | CRC, | HCT116 | - | in-vitro, | CRC, | HCT116 |
| 2581- | ART/DHA, | PB, | Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells |
| - | in-vitro, | AML, | NA |
| 2580- | ART/DHA, | VitC, | Effects of Antioxidants and Pro-oxidants on Cytotoxicity of Dihydroartemisinin to Molt-4 Human Leukemia Cells |
| - | in-vitro, | AML, | NA |
| 2578- | ART/DHA, | RES, | Synergic effects of artemisinin and resveratrol in cancer cells |
| - | in-vitro, | Liver, | HepG2 | - | in-vitro, | Cerv, | HeLa |
| 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 |
| 2576- | ART/DHA, | AL, | The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo |
| - | in-vitro, | OS, | MG63 | - | in-vivo, | NA, | NA |
| 2575- | ART/DHA, | docx, | Artemisia santolinifolia-Mediated Chemosensitization via Activation of Distinct Cell Death Modes and Suppression of STAT3/Survivin-Signaling Pathways in NSCLC |
| - | in-vitro, | Lung, | H23 |
| 2574- | ART/DHA, | Artemisinin: A Promising Adjunct for Cancer Therapy |
| - | Review, | Var, | NA |
| 2573- | ART/DHA, | Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells |
| - | in-vitro, | CRC, | HCT116 |
| 2572- | ART/DHA, | SRF, | Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax |
| - | in-vitro, | AML, | NA |
| 2571- | ART/DHA, | Cancer combination therapies with artemisinin-type drugs |
| - | Review, | Var, | NA |
| 2570- | ART/DHA, | Discovery, mechanisms of action and combination therapy of artemisinin |
| - | Review, | Nor, | NA |
| 555- | ART/DHA, | Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action |
| - | Review, | NA, | NA |
| 3395- | ART/DHA, | Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis |
| - | in-vitro, | NA, | HSC-T6 |
| 4993- | ART/DHA, | Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway |
| - | vitro+vivo, | GC, | NA |
| 4992- | ART/DHA, | Dihydroartemisinin Increases the Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via the Nrf2/HO-1 Anti-Oxidant Signaling Pathway |
| - | in-vitro, | AML, | HL-60 |
| 4991- | ART/DHA, | doxoR, | Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy |
| - | in-vivo, | Nor, | H9c2 |
| 4278- | ART/DHA, | Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway |
| - | in-vivo, | NA, | NA |
| 3667- | ART/DHA, | Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in microglia |
| - | Review, | Sepsis, | NA |
| 3666- | ART/DHA, | Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling |
| - | NA, | AD, | NA |
| 3665- | ART/DHA, | Artemisinin B Improves Learning and Memory Impairment in AD Dementia Mice by Suppressing Neuroinflammation |
| - | Review, | AD, | NA |
| 3396- | ART/DHA, | Progress on the study of the anticancer effects of artesunate |
| - | Review, | Var, | NA |