Database Query Results : Artemisinin, ,

ART/DHA, Artemisinin: Click to Expand ⟱
Features:

Artemisinin — a plant-derived sesquiterpene lactone endoperoxide (from Artemisia annua) best known as the parent scaffold for artemisinin-class antimalarials and widely investigated as a tumor-selective redox/iron-reactive cytotoxic agent. It is a small-molecule natural product (drug-like phytochemical) whose major clinical derivatives include artesunate (water-soluble), artemether/arteether (lipophilic), and the active metabolite dihydroartemisinin (DHA). In oncology literature the abbreviation set commonly includes ART (artemisinin), AS (artesunate), and DHA (dihydroartemisinin); many mechanistic claims are derivative-specific and exposure/iron-context dependent.

Primary mechanisms (ranked):

  1. Iron-dependent activation of the endoperoxide bridge causing ROS/lipid peroxidation stress and tumor-selective cytotoxicity (iron-high contexts)
  2. Ferroptosis sensitization/induction via iron handling and lipid peroxidation programs (often linked to ferritin/lysosome biology; context-dependent)
  3. Mitochondrial dysfunction with ΔΨm loss and intrinsic apoptosis signaling (downstream of oxidative stress)
  4. ER stress / UPR activation (stress-amplification axis)
  5. Hypoxia–metabolism suppression (HIF-1α and glycolysis program attenuation; model-dependent)
  6. Pro-survival inflammatory signaling suppression (e.g., NF-κB / STAT3 axes; model-dependent)

Bioavailability / PK relevance: Oral artemisinin has variable and generally limited systemic exposure with a short half-life on the order of hours; many anticancer in-vitro concentrations exceed typical achievable free-plasma levels without formulation strategies. Artesunate is rapidly converted to DHA; in an FDA label dataset (IV artesunate for severe malaria), artesunate has a very short half-life (~0.3 h) and DHA ~1.3 h, emphasizing exposure-time constraints and the need to interpret “ART/AS/DHA” PK separately.

In-vitro vs systemic exposure relevance: Many reported anticancer effects are driven by oxidative stress at micromolar in-vitro conditions and may be difficult to reproduce systemically without targeted delivery, local administration, or combination strategies that increase intratumoral iron/ROS burden (context-dependent).

Clinical evidence status: Cancer use remains investigational (preclinical-dominant with small/early human studies). Multiple registered clinical studies have evaluated artesunate/derivatives in oncology settings (e.g., phase I solid tumor IV artesunate; small/phase II-style neoadjuvant/adjunct trials), but there is no major regulatory approval for cancer indications; artesunate is approved/used clinically for severe malaria.

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

Artemisinin-class (ART/AS/DHA) mechanisms relevant to cancer biology

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Iron-activated endoperoxide chemistry and ROS burden ROS↑, lipid peroxidation↑, macromolecular damage↑ (iron-high contexts) ROS↔ to ↑ (dose-dependent) P Pro-oxidant, tumor-biased cytotoxic stress Core premise: iron availability (labile iron pool, heme/Fe²⁺ context) gates potency and selectivity; derivative and formulation matter.
2 Ferroptosis susceptibility Ferroptosis↑ (context-dependent), lipid-ROS↑ Ferroptosis↔ (context-dependent) R Non-apoptotic death program engagement or sensitization Evidence supports artemisinin-compounds as ferroptosis sensitizers/inducers in multiple models; often tied to iron handling and lipid peroxidation control nodes.
3 Ferritin and lysosome axis Ferritin turnover↑ / lysosomal iron↑ (model-dependent) → ROS↑ ↔ (model-dependent) R Iron mobilization that amplifies oxidative injury DHA/derivatives have been reported to engage ferritin/lysosome-related processes that increase reactive iron, supporting ferroptotic and apoptotic stress amplification.
4 Mitochondria and MPTP ΔΨm↓, mitochondrial ROS↑, Cyt-c release↑, apoptosis↑ Stress responses↔ to ↑ (dose-dependent) R Intrinsic apoptosis downstream of redox injury Mitochondrial impairment is commonly reported as a downstream execution route after ROS/iron activation; can intersect with ferroptosis via redox spillover.
5 ER stress and UPR ER stress↑, UPR↑ ↔ to ↑ (stress-dose dependent) R Proteostasis collapse / stress signaling Often co-occurs with ROS-driven injury; may contribute to growth arrest and death pathway crosstalk.
6 HIF-1α axis HIF-1α↓ (model-dependent) ↔ G Anti-hypoxic adaptation Reported suppression of hypoxia programs may reduce angiogenic and glycolytic adaptation in some tumors.
7 Glycolysis and glucose transport Glycolysis↓, GLUT1/HK2/PKM2↓ (model-dependent) ↔ (context-dependent) G Metabolic constraint Metabolic effects vary by cell state; can synergize with glycolysis inhibitors in model systems.
8 STAT3 axis STAT3↓ (model-dependent) ↔ G Pro-survival transcriptional attenuation Reported in subsets of studies; may contribute to reduced proliferation/survival signaling.
9 NF-κB and inflammatory signaling NF-κB↓, inflammatory cytokine programs↓ (model-dependent) Inflammation↓ (context-dependent) G Anti-inflammatory / pro-differentiation pressure Can be beneficial for tumor microenvironment modulation, but directionality and net effect depend on immune context.
10 NRF2 axis NRF2↔ (model-dependent; adaptive resistance possible) NRF2↔ to ↑ (context-dependent) G Redox adaptation gatekeeper NRF2 status can determine sensitivity vs resistance to ROS/ferroptosis; combinations that blunt NRF2 defenses are often proposed experimentally.
11 Clinical Translation Constraint Short exposure window; achievable concentrations may be below many in-vitro active ranges; heterogeneity in iron/redox state; derivative-specific PK Off-target oxidative stress risk (dose/formulation dependent) G Limits systemic reproducibility Interpret ART vs AS vs DHA separately; artesunate→DHA conversion is rapid and half-lives are short (route-dependent). Targeted delivery and combination strategies are common translational approaches.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
Scientific Papers found: Click to Expand⟱
4438- AgNPs,  ART/DHA,    Biogenic synthesis of AgNPs using Artemisia oliveriana extract and their biological activities for an effective treatment of lung cancer
- in-vitro, Lung, A549
"highlight2" >EPR↑, cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell.
"highlight2" >BAX↑, Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9)
"highlight2" >Bcl-2↑,
"highlight2" >Casp3↑,
"highlight2" >Casp9↑,
"highlight2" >DNAdam↑, apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line.
"highlight2" >TumCCA↑,
"highlight2" >Apoptosis↑,

4552- AgNPs,  ART/DHA,    Green synthesis of silver nanoparticles using Artemisia turcomanica leaf extract and the study of anti-cancer effect and apoptosis induction on gastric cancer cell line (AGS)
- in-vitro, GC, AGS
"highlight2" >AntiCan↑, iologically synthesized silver nanoparticles induced apoptosis, and showed a cytotoxic and anti-cancer effect against gastric cancer cell lines in a dose- and time-dependent manner.
"highlight2" >Apoptosis↑,
"highlight2" >eff↑, Biologically synthesized nanoparticles may possess higher anti-cancer properties than commercial silver

3388- ART/DHA,    Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation
- in-vitro, Lung, A549 - in-vitro, Nor, GP-293 - in-vitro, BC, MDA-MB-231
"highlight2" >NRF2↑, ATT upregulated Nrf2 in the MB231 cells . ATT increased Nrf2 levels at low doses ranging from 1 to 5 μM
"highlight2" >ROS∅, ATT does not increase ROS production and cannot active Nrf2 by inducing oxidative stress

3666- ART/DHA,    Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling
- NA, AD, NA
"highlight2" >*Inflam↓, Artemisinin has potent anti-inflammatory and immune activities.
"highlight2" >*neuroP↑, Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway.
"highlight2" >*TLR4↓,
"highlight2" >*NF-kB↓,
"highlight2" >*memory↑, reversing spatial learning and memory deficits.
"highlight2" >*ROS↓, Artemisinin Decreased the Production of ROS and iNOS in BV2 Cells
"highlight2" >*iNOS↓,
"highlight2" >*COX2↓, Artemisinin treatment decreased the expression of COX2 and iNOS
"highlight2" >*cognitive↑, Artemisinin Improved the Cognitive Impairment of AD Model Mice

3665- ART/DHA,    Artemisinin B Improves Learning and Memory Impairment in AD Dementia Mice by Suppressing Neuroinflammation
- Review, AD, NA
"highlight2" >*Inflam↓, artemisinin B from Artemisia annua Linn. has strong anti-inflammatory and immunological activities.
"highlight2" >*NO↓, artemisinin B inhibited NO secretion from LPS-induced BV2 cells and significantly reduced the expression levels of the inflammatory cytokines IL-1β, IL-6 and TNF-α.
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*TNF-α↓,
"highlight2" >*MyD88↓, accompanied by reduced gene expression levels of MyD88 and NF-κB as well as TLR4 and MyD88 protein levels
"highlight2" >*NF-kB↓,
"highlight2" >*TLR4↓,
"highlight2" >*memory↑, artemisinin B improved spatial memory in dementia mice in the water maze and step-through tests

3396- ART/DHA,    Progress on the study of the anticancer effects of artesunate
- Review, Var, NA
"highlight2" >TumCP↓, reported inhibitory effects on cancer cell proliferation, invasion and migration.
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >Apoptosis↑, ART has been reported to induce apoptosis, differentiation and autophagy in colorectal cancer cells by impairing angiogenesis
"highlight2" >Diff↑,
"highlight2" >TumAuto↑,
"highlight2" >angioG↓,
"highlight2" >TumCCA↑, inducing cell cycle arrest (11), upregulating ROS levels, regulating signal transduction [for example, activating the AMPK-mTOR-Unc-51-like autophagy activating kinase (ULK1) pathway in human bladder cancer cells]
"highlight2" >ROS↑,
"highlight2" >AMPK↑,
"highlight2" >mTOR↑,
"highlight2" >ChemoSen↑, ART has been shown to restore the sensitivity of a number of cancer types to chemotherapeutic drugs by modulating various signaling pathways
"highlight2" >Tf↑, ART could upregulate the mRNA levels of transferrin receptor (a positive regulator of ferroptosis), thus inducing apoptosis and ferroptosis in A549 non-small cell lung cancer (NSCLC) cells.
"highlight2" >Ferroptosis↑,
"highlight2" >Ferritin↓, ferritin degradation, lipid peroxidation and ferroptosis
"highlight2" >lipid-P↑,
"highlight2" >CDK1↑, Cyclin-dependent kinase 1, 2, 4 and 6
"highlight2" >CDK2↑,
"highlight2" >CDK4↑,
"highlight2" >CDK6↑,
"highlight2" >SIRT1↑, Sirt1 levels
"highlight2" >COX2↓,
"highlight2" >IL1β↓, IL-1? ?
"highlight2" >survivin↓, ART can selectively downregulate the expression of survivin and induce the DNA damage response in glial cells to increase cell apoptosis and cell cycle arrest, resulting in increased sensitivity to radiotherapy
"highlight2" >DNAdam↑,
"highlight2" >RadioS↑,

3395- ART/DHA,    Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis
- in-vitro, NA, HSC-T6
"highlight2" >*Ferroptosis↑, Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro
"highlight2" >*GSH↓,
"highlight2" >*ROCK1↓, Interestingly, the ROCK1 protein level was significantly reduced after Art treatment compared with ROCK2, which raised the probability that ROCK1 was involved in the regulation of ferroptosis in LX2 cells

3394- ART/DHA,    Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine
"highlight2" >IGF-1R↓, Artemisinin downregulated IGF-IR expression and inhibited the growth of MCF-7 breast tumor cell xenografts in nude mice

3393- ART/DHA,    Artemisinin-derived artemisitene blocks ROS-mediated NLRP3 inflammasome and alleviates ulcerative colitis
- in-vivo, Col, NA
"highlight2" >*ROS↓, Artemisitene inhibits ROS (especially mtROS) production and NLRP3 inflammasome assembly.
"highlight2" >*NLRP3↓,
"highlight2" >*Inflam↓, artemisitene significantly attenuated inflammatory response in DSS-induced ulcerative colitis

3392- ART/DHA,    Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways
- in-vitro, Nor, Hep3B - in-vivo, NA, NA
"highlight2" >*Inflam↓, anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice.
"highlight2" >*NF-kB↓, artemisinin significantly inhibited the expression of NF-?B reporter gene induced by TNF-? in a dose-dependent manner
"highlight2" >*ROS↓, artemisinin significantly impaired the ROS production and phosphorylation of p38 and ERK,
"highlight2" >*p‑p38↓,
"highlight2" >*p‑ERK↓,

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
"highlight2" >TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
"highlight2" >TumMeta↓,
"highlight2" >angioG↓,
"highlight2" >TumVol↓, reduces tumor volume and progression
"highlight2" >BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
"highlight2" >Half-Life↓,
"highlight2" >BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
"highlight2" >eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
"highlight2" >eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
"highlight2" >ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
"highlight2" >selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
"highlight2" >TumCCA↑, G2/M, decreased survivin
"highlight2" >survivin↓,
"highlight2" >BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
"highlight2" >Casp3↓,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >CDC25↓,
"highlight2" >CycB/CCNB1↓,
"highlight2" >NF-kB↓,
"highlight2" >cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
"highlight2" >cycE/CCNE↓,
"highlight2" >E2Fs↓,
"highlight2" >P21↑,
"highlight2" >p27↑,
"highlight2" >ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
"highlight2" >MDM2↓,
"highlight2" >VEGF↓, Decreased VEGF
"highlight2" >IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
"highlight2" >COX2↓,
"highlight2" >MMP9↓,
"highlight2" >ER Stress↓, ER stress, degradation of c-MYC
"highlight2" >cMyc↓,
"highlight2" >GRP78/BiP↑, Increased GRP78
"highlight2" >DNAdam↑, DNA damage
"highlight2" >AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
"highlight2" >MMP2↓,
"highlight2" >PKCδ↓,
"highlight2" >Raf↓,
"highlight2" >ERK↓,
"highlight2" >JNK↓,
"highlight2" >PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >TOP2↓, Inhibition of topoisomerase II a
"highlight2" >uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
"highlight2" >MMP7↓,
"highlight2" >TIMP2↑, Increased TIMP2, Cdc42, E cadherin
"highlight2" >Cdc42↑,
"highlight2" >E-cadherin↑,

3390- ART/DHA,    Ferroptosis: The Silver Lining of Cancer Therapy
"highlight2" >Ferroptosis↑, Artesunate induces ferroptosis in tumour cells by enhancing lysosomal activity and increasing lysosomal iron concentration
"highlight2" >Iron↑,
"highlight2" >NCOA4↝, Artesunate regulates ferroptosis by promoting ferritinophagy by regulating the gene expression of NCOA4, which leads to an increase in the iron levels
"highlight2" >ROS↑, overproduction of ROS triggered by the Fenton reaction between iron ion and hydrogen peroxide is a crucial factor for inducing ferroptosis.
"highlight2" >Fenton↑,
"highlight2" >Tf↓, artesunate can induce ferroptosis in Adriamycin-resistant leukaemia cells by decreasing TF levels

3389- ART/DHA,    Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers
- Review, Var, NA
"highlight2" >GSH↓, decreasing cellular GSH levels and the presence of iron-induced ROS generation
"highlight2" >ROS↑,
"highlight2" >NRF2↑, However, ART-mediated killing of cisplatin-resistant HNC cells can simultaneously activate the NRF2-antioxidant response element (ARE) pathway, which contributes to ferroptosis resistance
"highlight2" >eff↑, Therefore, the combination of ART with NRF2 genetic silencing or trigonelline may provide a preferable efficacy

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
"highlight2" >*IL6↓, ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression.
"highlight2" >*Casp3↓,
"highlight2" >*Casp9↓,
"highlight2" >*BDNF↑,
"highlight2" >*ERK↑,
"highlight2" >*NRF2↑,
"highlight2" >*HO-1↑,
"highlight2" >*neuroP↑, ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.
"highlight2" >*antiOx↑,
"highlight2" >*Inflam↓,

3387- ART/DHA,    Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment
- Review, Var, NA
"highlight2" >BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
"highlight2" >lipid-P↑, promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo.
"highlight2" >Ferroptosis↑,
"highlight2" >Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
"highlight2" >GPx4↓, GPX4-dependent defense system is significantly inhibited
"highlight2" >GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
"highlight2" >P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
"highlight2" >ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
"highlight2" >PERK↑,
"highlight2" >ATF4↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >CHOP↑, which activates CHOP
"highlight2" >ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
"highlight2" >NRF2↑, ARTEs can activate the nuclear factor erythroid-derived 2-like 2 (Nrf2) -γ-glutamyl-peptide pathway in cancer cells, resulting in cancer cell ferroptosis resistance

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
"highlight2" >*MDA↑, Table 1 normal vs art
"highlight2" >*SOD↓, Table 2 normal vs art
"highlight2" >*GSH∅, Table 3 normal vs art (slight increase)
"highlight2" >*Catalase↓, table 4 normal vs art

3385- ART/DHA,    Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study
- Study, NA, NA
"highlight2" >*NF-kB↑, protective role of derivative of ART was observed in asthma condition where restoration of three fold reduced catalase activity was found by promoting Nuclear factor erythroid-2-related factor (Nrf2)
"highlight2" >*Catalase↑,

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
"highlight2" >Ferroptosis↑, DHA displayed classic features of ferroptosis, such as increased lipid reactive oxygen species
"highlight2" >ROS↑,
"highlight2" >GSH↓, decreased activity or expression of glutathione (GSH), glutathione peroxidase 4, solute carrier family (SLC) 7 member 11 and SLC family 3 member 2.
"highlight2" >UPR↑, DHA activated all three branches of the UPR
"highlight2" >GPx4↓, GSH depletion leads to the suppression of glutathione peroxidase (GPX)4, a key glutathione peroxidase known to catalyze the reduction of lipid ROS
"highlight2" >PERK↑, DHA was found to activate PERK/eIF2α/ATF4
"highlight2" >eIF2α↑,
"highlight2" >ATF4↑,

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
"highlight2" >TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
"highlight2" >Apoptosis↑,
"highlight2" >TumMeta↓,
"highlight2" >angioG↓,
"highlight2" >TumAuto↑,
"highlight2" >ER Stress↑,
"highlight2" >ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
"highlight2" >Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
"highlight2" >p38↑,
"highlight2" >HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
"highlight2" >PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
"highlight2" >GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
"highlight2" >Glycolysis↓, Inhibited glycolysis
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >Hif1a↓,
"highlight2" >PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
"highlight2" >lactateProd↓,
"highlight2" >GlucoseCon↓,
"highlight2" >EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
"highlight2" >Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
"highlight2" >Zeb1↓,
"highlight2" >ZEB2↓,
"highlight2" >Twist↓,
"highlight2" >Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
"highlight2" >CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
"highlight2" >TGF-β↓,
"highlight2" >p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
"highlight2" >M2 MC↓,
"highlight2" >uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
"highlight2" >HH↓, via inhibiting the hedgehog signaling pathway
"highlight2" >AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
"highlight2" >VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
"highlight2" >JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
"highlight2" >Beclin-1↑,
"highlight2" >GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
"highlight2" >eff↑, results demonstrated that DHA-induced ER stress required iron
"highlight2" >eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
"highlight2" >eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
"highlight2" >eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
"highlight2" >eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
"highlight2" >eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
"highlight2" >IL4↓, downregulated IL-4;
"highlight2" >DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
"highlight2" >Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
"highlight2" >Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
"highlight2" >FADD↑,
"highlight2" >cl‑PARP↑,
"highlight2" >cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >Mcl-1↓, Downregulated Mcl-1
"highlight2" >Ki-67↓, Downregulated Ki-67 and Bcl-2
"highlight2" >Bcl-2↓,
"highlight2" >CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
"highlight2" >VEGF↓, Downregulated VEGF, COX-2 and MMP-9
"highlight2" >COX2↓,
"highlight2" >MMP9↓,

3382- ART/DHA,    Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?
- Review, Var, NA
"highlight2" >AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
"highlight2" >toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
"highlight2" >Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
"highlight2" >ROS↑,
"highlight2" >TumCCA↑,
"highlight2" >BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
"highlight2" >eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
"highlight2" >Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
"highlight2" >Ferritin↓, Figure 3
"highlight2" >GPx4↓,
"highlight2" >NADPH↓,
"highlight2" >GSH↓,
"highlight2" >BAX↑,
"highlight2" >Cyt‑c↑,
"highlight2" >cl‑Casp3↑,
"highlight2" >VEGF↓, angiogenesis
"highlight2" >IL8↓,
"highlight2" >COX2↓,
"highlight2" >MMP9↓,
"highlight2" >E-cadherin↑,
"highlight2" >MMP2↓,
"highlight2" >NF-kB↓,
"highlight2" >p16↑, cell cycle arrest
"highlight2" >CDK4↓,
"highlight2" >cycD1/CCND1↓,
"highlight2" >p62↓, autophagy
"highlight2" >LC3II↑,
"highlight2" >EMT↓, suppressing EMT and CSCs
"highlight2" >CSCs↓,
"highlight2" >Wnt↓, Depress Wnt/β-catenin signaling pathway
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >uPA↓, Inhibit u-PA activity, protein and mRNA expression
"highlight2" >TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
"highlight2" >angioG↓, Inhibition of Angiogenesis
"highlight2" >ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

3345- ART/DHA,    Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells
- in-vitro, GBM, NA
"highlight2" >ROS↑, Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death
"highlight2" >Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
"highlight2" >lipid-P↑,
"highlight2" >HSP70/HSPA5↑, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5)
"highlight2" >ER Stress↑, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4)
"highlight2" >ATF4↑,
"highlight2" >GRP78/BiP↑, HSPA5
"highlight2" >MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
"highlight2" >GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
"highlight2" >eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
"highlight2" >GPx4↑, DHA induced-ER stress in turn activated cell protection against ferroptosis through PERK-ATF4- HSPA5 activation, which promoted the expression of GPX4 to detoxify peroxidized membrane lipids

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
"highlight2" >eff↑, Guided by this mechanism, the specific cytotoxicity of ART toward CRC cells can be dramatically enhanced with the addition of aminolevulinic acid (ALA), a clinically used heme synthesis precursor, to increase heme levels
"highlight2" >ROS↑, We found that artesunate significantly increased ROS levels (Figure 4f) in HCT116 cells
"highlight2" >selectivity↑, In contrast, heme levels in normal cells and tissues are strictly controlled and maintained at lower levels, minimizing ART’s activation, which could possibly explain the specificity and low toxicity of ART.
"highlight2" >TumCG↓, Strikingly, the combination of artesunate and ALA showed significant tumor growth delay in comparison to both the control and the artesunate or ALA single treatment groups
"highlight2" >toxicity↓, Since both artesunate and ALA are clinically used and well-tolerated, (52) this combination has the potential to be safely applied to subsequent clinical testing

2581- ART/DHA,  PB,    Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells
- in-vitro, AML, NA
"highlight2" >eff↑, The combination of 20 microM DHA and 1 mM sodium butyrate killed all Molt-4 cells at the 24-hour time-point and did not significantly affect lymphocytes.
"highlight2" >selectivity↑,

2580- ART/DHA,  VitC,    Effects of Antioxidants and Pro-oxidants on Cytotoxicity of Dihydroartemisinin to Molt-4 Human Leukemia Cells
- in-vitro, AML, NA
"highlight2" >eff↓, Compared to control, ascorbate and H 2 O 2 both caused a significant decrease in cell count both at 24-h (p<0.05 and p<0.0001 for ascorbate and H 2 O 2 , respectively)
"highlight2" >other↝, Vitamin C, a common supplement, has been shown to act as both a ROS generator in the presence of iron and copper (15) and as an antioxidant
"highlight2" >ROS↑, From our results, we can postulate that ROS generation is causing cell death independently and in combination with DHA
"highlight2" >eff↓, Ascorbate can convert ferric iron into ferrous iron (18), the active form that reacts with artemisinin, generating short lived free radicals.
"highlight2" >eff↓, If this happens in the stomach of a person who is consuming artemisinin along with ascorbate, ascorbate will convert ferric iron in foods to the ferrous form, which may react with artemisinin locally, making the therapy less effective

555- ART/DHA,    Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action
- Review, NA, NA
"highlight2" >STAT3↓, potential direct inhibitor of STAT3

5135- ART/DHA,    Dihydroartemisinin Inhibits mTORC1 Signaling by Activating the AMPK Pathway in Rhabdomyosarcoma Tumor Cells
- vitro+vivo, Var, NA
"highlight2" >mTORC1↓, Dihydroartemisinin (DHA), an anti-malarial drug, has been shown to possess potent anticancer activity, partly by inhibiting the mammalian target of rapamycin (mTOR) complex 1 (mTORC1)
"highlight2" >AMPK↑, DHA activated AMP-activated protein kinase (AMPK).
"highlight2" >TumCG↓, treatment with artesunate, a prodrug of DHA, dose-dependently inhibited tumor growth and concurrently activated AMPK and suppressed mTORC1 in RMS xenografts.

5383- ART/DHA,    Artesunate is a drug used to treat severe malaria.
- Review, Var, NA
"highlight2" >Half-Life?, The elimination half life of artesunate is 0.3h with a range of 0.1-1.8h.8 The elimination half life of DHA is 1.3h with a range of 0.9-2.9h.8 Half life after intramuscular administration is 48 min in children and 41 min in adults

5382- ART/DHA,    A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies
- Trial, Var, NA
"highlight2" >AntiCan↑, The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models.
"highlight2" >Dose↝, maximum tolerated dose (MTD) . maximum tolerated dose (MTD) a
"highlight2" >Dose↝, MTD of intravenous artesunate is 18 mg/kg

5381- ART/DHA,    Artemisitene triggers calcium-dependent ferroptosis by disrupting the LSH-EWSR1 interaction in colorectal cancer
- in-vitro, CRC, HCT116 - in-vitro, Nor, NCM460 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT8
"highlight2" >Ferroptosis↑, Artemisia annua, acted as a CRC therapeutic agent by promoting calcium-dependent ferroptosis.
"highlight2" >CYP24A1↓, ATT repressed cytochrome P450 family 24 subfamily A member 1 (CYP24A1) expression, the pivotal mediator of this response
"highlight2" >Ca+2↑, ATT downregulated CYP24A1 expression to elevate calcium levels and induce ferroptosis in CRC cells
"highlight2" >SCD1↓, The ensuing calcium overload downregulated stearoyl-CoA desaturase (SCD) by CAMKK2/AMPK/SREBF1 axis, enriching oxidizable fatty acids and sensitizing CRC cells to lethal lipid peroxidation.
"highlight2" >FAO↑,
"highlight2" >lipid-P↑,
"highlight2" >eff↑, The results showed that ATT exhibited the highest cytotoxicity, surpassing that of dihydroartemisinin and artesunate, whereas artemisinin and artemether were only weakly effective
"highlight2" >selectivity↑, ATT induced cell death in a strictly time-dependent manner and displayed minimal toxicity toward normal NCM460 epithelial cells
"highlight2" >other?, Collectively, these data reveal that ATT-driven calcium overload disrupts fatty-acid homeostasis via SCD inhibition, thereby steering CRC cells toward ferroptosis.

5380- ART/DHA,    Artemisinin and Its Derivatives as Potential Anticancer Agents
- Review, Var, NA
"highlight2" >TumCG↓, Artemisinin (1, Figure 2) could suppress cell growth [16], reduce angiogenesis-related factors [17], and induce ferroptosis [18] in breast cancer cell lines
"highlight2" >angioG↓,
"highlight2" >Ferroptosis↑,
"highlight2" >TumCP↑, Dihydroartemisinin (2, Figure 2) exhibited anticancer effects against breast cancer by suppressing cell proliferation [16], inhibiting angiogenesis [19], inducing autophagy [20] and pyroptosis [21], and targeting cancer stem cells (CSCs) [
"highlight2" >TumAuto↑,
"highlight2" >CSCs↑,
"highlight2" >eff↑, Dihydroartemisinin is more potent than artemisinin, as the IC50 values at 24 h were lower on MCF-7 (129.1 μM versus 396.6 μM) and MDA-MB-231 (62.95 μM versus 336.63 μM)
"highlight2" >YAP/TEAD↓, Additionally, dihydroartemisinin was proven to have the ability to reduce the expression of yes-associated protein 1 (YAP1), which has been commonly used as a prognostic marker in liver cancer.
"highlight2" >TumCCA↑, induced G0/G1 cell cycle arrest and apoptosis by promoting oxygen species (ROS) accumulation.
"highlight2" >ROS↑,
"highlight2" >ChemoSen↑, The application of combination treatment using artemisinin and its derivatives with commonly used chemotherapy drugs, such as cisplatin, carboplatin, doxorubicin, temozolomide, etc., always exhibits significantly improved anticancer effects
"highlight2" >N-cadherin↓, and inhibiting the proliferation, colony formation, and invasiveness of colon cancer cells by inhibiting NRP2, N-cadherin, and Vimentin expression
"highlight2" >Vim↓,
"highlight2" >MMP9↓, by decreasing the expression of HuR and matrix metalloproteinase (MMP)-9 proteins [24],
"highlight2" >eff↑, Further investigations suggested that both dihydroartemisinin treatment and the loss of PRIM2 could lead to a decreased GSH level and induce cellular lipid ROS and mitochondrial MDA expression.
"highlight2" >STAT3↓, Recently, artemisinin and its derivatives were reported to have potential as direct STAT3 inhibitors [98].
"highlight2" >CD133↓, dihydroartemisinin treatment could significantly reduce the expression of CSC markers (CD133, CD44, Nanog, c-Myc, and OCT4) by downregulating Akt/mTOR pathway
"highlight2" >CD44↓,
"highlight2" >Nanog↓,
"highlight2" >cMyc↓,
"highlight2" >OCT4↓,
"highlight2" >Akt↓,
"highlight2" >mTOR↓,

5379- ART/DHA,    Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance—from immune microenvironment crosstalk to therapeutic translation
"highlight2" >Ferritin↓, dihydroartemisinin (DAT, which triggers lysosomal ferritin degradation).
"highlight2" >Iron↑, DAT has shown promise in reversing carboplatin resistance in ovarian cancer cell lines by expanding the labile iron pool (LIP) and enhancing Fenton reaction-mediated lipid peroxidation (149).
"highlight2" >Fenton↑,
"highlight2" >lipid-P↑,
"highlight2" >ChemoSen↑, Its advantage lies in synergistic effects with conventional chemotherapies, as iron overload amplifies chemotherapy-induced oxidative stress.
"highlight2" >ROS↑,
"highlight2" >eff↝, However, DAT requires careful monitoring of systemic iron levels to avoid anemia, and its efficacy is reduced in cancer cells with upregulated ferroportin (an iron export protein).

5378- ART/DHA,    Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives
- Review, Var, NA
"highlight2" >Ferroptosis↑, Artemisinin increases ferroptosis risk in cancer cells by increasing cellular free iron and lipid peroxidation, causing increased membrane permeability and decreased integrity [59]
"highlight2" >Iron↑,
"highlight2" >lipid-P↑,
"highlight2" >MOMP↑,
"highlight2" >AntiCan↑, Artemisinin has anticancer and antimalarial properties by upregulating NCOA4 and DMT1 levels, raising ferrous ion levels, and causing ferroptosis by downregulating GSH and GPX4 levels [30, 59, 75].
"highlight2" >NCOA4↑,
"highlight2" >GSH↓,
"highlight2" >GPx4↓,
"highlight2" >ROS↑, Artemisinin and its derivatives regulate 20 iron metabolism genes, thereby causing the formation of ROS [76]
"highlight2" >ChemoSen↑, Artesunate, when combined with sorafenib, can enhance the susceptibility of hepatocellular carcinoma cells to cisplatin resistance through ferroptosis inhibition [77].
"highlight2" >ER Stress↑, artemisinin, specifically ferroptosis, by controlling iron metabolism, producing ROS, and triggering ER‐stress.
"highlight2" >DNAdam↑, primary antineoplastic mechanisms of artemisinin are ferroptosis, DNA damage, tumour angiogenesis suppression and cell cycle inhibition [78]
"highlight2" >angioG↓,
"highlight2" >TumCCA↑,
"highlight2" >eff↓, while NAC and ferrostatin‐1 partially reverse these effects [82]

5377- ART/DHA,    Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein
- in-vitro, AML, NA
"highlight2" >AntiCan↑, Artemisinin is an anti-malarial drug that has shown anticancer properties
"highlight2" >Ferroptosis↑, Recently, ferroptosis was reported to be induced by dihydroartemisinin (DHA) and linked to iron increase.
"highlight2" >Iron↑, We found that treatment of DHA induces early ferroptosis by promoting ferritinophagy and subsequent iron increase.
"highlight2" >Mets↑, Furthermore, our study demonstrated that DHA activated zinc metabolism signaling, especially the upregulation of metallothionein (MT).
"highlight2" >eff↑, Supportingly, we showed that inhibition MT2A and MT1M isoforms enhanced DHA-induced ferroptosis.
"highlight2" >GSH↝, Finally, we demonstrated that DHA-induced ferroptosis alters glutathione pool, which is highly dependent on MTs-driven antioxidant response.
"highlight2" >eff↑, DHA cooperates with FAC to increase the intracellular iron pool. ferric citrate iron (FAC)
"highlight2" >other↓, Under oxidative stress, MT can release Zn2+ (apo-MT) to form thiol groups and participates in GSSG/ GSH reduction.
"highlight2" >eff↑, Our current findings also suggest that MT chemical inhibition can cooperate with DHA in primary AML cells in patients.
"highlight2" >other↓, Subsequent MT inhibition may sensitize leukemic cells to lipid peroxidation in vitro by impairing GSH regeneration.

5376- ART/DHA,    Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, SW48 - in-vitro, BC, MDA-MB-453
"highlight2" >Ferroptosis↑, artemisinin compounds can sensitize cancer cells to ferroptosis, a new form of programmed cell death driven by iron-dependent lipid peroxidation.
"highlight2" >Ferritin↓, Mechanistically, dihydroartemisinin (DAT) can induce lysosomal degradation of ferritin in an autophagy-independent manner, increasing the cellular free iron level and causing cells to become more sensitive to ferroptosis.
"highlight2" >Iron↑,
"highlight2" >eff↑, we found that DAT can augment GPX4 inhibition-induced ferroptosis
"highlight2" >TumAuto↑, DAT sensitizes cells to ferroptosis by stimulating autophagy.
"highlight2" >LC3II↑, it caused an increase of LC3-II production
"highlight2" >ROS↑, DAT increases lipid ROS and sensitizes cancer cells to ferroptosis

5137- ART/DHA,    Autophagy-dependent cell cycle arrest in esophageal cancer cells exposed to dihydroartemisinin
- vitro+vivo, ESCC, Eca109
"highlight2" >tumCV↓, Our results proved that DHA significantly reduced the viability of Eca109 cells in a dose- and time-dependent manner.
"highlight2" >TumCCA↑, DHA evidently induced cell cycle arrest at the G2/M phase in Eca109 cells
"highlight2" >ROS↑, Mechanistically, DHA induced intracellular ROS generation and autophagy in Eca109 cells
"highlight2" >TumAuto↑,
"highlight2" >eff↓, blocking ROS by an antioxidant NAC obviously inhibited autophagy
"highlight2" >TRF2↓, we found that telomere shelterin component TRF2 was down-regulated in Eca109 cells exposed to DHA through autophagy-dependent degradation
"highlight2" >TumCP↓, DHA inhibits the proliferation ability of Eca109 cells in vitro and in vivo

5136- ART/DHA,    Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis
- in-vitro, Var, NA
"highlight2" >angioG↓, The anti-malarial agent dihydroartemisinin (DHA) has strong anti-angiogenic activity.
"highlight2" >TumCP↓, DHA shows a dose-dependent inhibition of proliferation and migration of in HUVECs.
"highlight2" >TumCMig↓,
"highlight2" >NF-kB↓, Our data suggested that DHA inhibits angiogenesis largely through repression of the NF-κB pathway.

3667- ART/DHA,    Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in microglia
- Review, Sepsis, NA
"highlight2" >*cognitive↑, artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests
"highlight2" >*neuroP↑, attenuated neuronal damage and microglial activation in the hippocampus.
"highlight2" >*TNF-α↓, artemisinin (40 μΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6)
"highlight2" >*IL6↓,
"highlight2" >*NF-kB↓, artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway;
"highlight2" >*AMPK↑,
"highlight2" >*ROS↓, artemisinin protects neuronal HT-22 cells from oxidative injury by activating the Akt pathway
"highlight2" >*Akt↑,
"highlight2" >*MCP1↓, artemisinin reversed the LPS-induced increases in the chemokines MCP-1 and MIP-2
"highlight2" >*MIP2↓,
"highlight2" >*TGF-β↑, Artemisinin also significantly increased the mRNA and protein expression of TGF-β
"highlight2" >*Inflam↓, The AMPKα1 pathway is involved in the anti-inflammatory effect of artemisinin

5134- ART/DHA,    Dihydroartemisinin induces autophagy by suppressing NF-κB activation
- in-vitro, Var, NA
"highlight2" >TumAuto↑, Dihydroartemisinin induces autophagy by suppressing NF-κB activation
"highlight2" >NF-kB↓,
"highlight2" >ChemoSen↑, DHA promotes autophagy in cancer cells and provide evidence for the DHA-induced sensitization effect of some chemotherapeutics

5133- ART/DHA,    Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
"highlight2" >AntiTum↑, (DHA) has been shown to exhibit anti-tumor activity in various cancer cells.
"highlight2" >tumCV↓, Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay.
"highlight2" >Apoptosis↓, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9.
"highlight2" >MMP↓,
"highlight2" >Cyt‑c↑,
"highlight2" >Casp9↑,
"highlight2" >CHOP↑, Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis
"highlight2" >GRP78/BiP↑,
"highlight2" >eIF2α↑,
"highlight2" >Casp12↑,
"highlight2" >ER Stress↑, DHA Induced Apoptosis through Mitochondria and Endoplasmic Reticulum (ER) Stress Pathways of Apoptosis in Human GBM Cells
"highlight2" >TumAuto↑, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy.
"highlight2" >ROS↑, Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy.

5132- ART/DHA,    Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
"highlight2" >Iron↓, In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners.
"highlight2" >TfR1/CD71↓, Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane.
"highlight2" >ROS↑, which may be a new action mechanism of DHA independently of oxidative damage.

5131- ART/DHA,    Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells
- in-vitro, NSCLC, ASTC-a-1
"highlight2" >Apoptosis↑, DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3
"highlight2" >MMP↓, DHA-induced loss of mitochondrial membrane potential (ΔΨm)
"highlight2" >Casp3↑,
"highlight2" >TumCP↓, proliferation of the cells could be effectively inhibited by DHA, even at a very low treating-dose (1 μg/ml) and a very short treating-time (12 h).

5130- ART/DHA,    Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway
- in-vitro, Bladder, T24/HTB-9
"highlight2" >tumCV↓, DHA significantly reduced cell viability in a dose-dependent manner.
"highlight2" >eff↓, Cytotoxicity of DHA was suppressed by N-acetylcysteine (NAC)
"highlight2" >Apoptosis↑, induction of cell apoptosis, which were manifested by annexin V-FITC staining, activation of caspase-3
"highlight2" >Casp3↑,
"highlight2" >ROS↑, DHA also increased ROS generation, cytochrome c release, and loss of mitochondrial transmembrane potential (ΔΨm) in cells.
"highlight2" >Cyt‑c↑,
"highlight2" >MMP↓,
"highlight2" >Bcl-2↓, downregulation of regulatory protein Bcl-2 and upregulation of Bax protein by DHA were also observed
"highlight2" >BAX↑,
"highlight2" >MOMP↑, Dihydroartemisinin increases mitochondrial permeability of EJ-138 and HTB-9 cells by Collapse of ΔΨm
"highlight2" >TumCG↓, It has shown that DHA selectively inhibits the growth of many cancer cells types, such as leukemia,[29] pancreas,[30] breast[31] and prostate[32] cancers

5129- ART/DHA,    Evidence for the Involvement of Carbon-centered Radicals in the Induction of Apoptotic Cell Death by Artemisinin Compounds
- in-vitro, AML, HL-60
"highlight2" >Casp↑, In HL-60 cells the endoperoxides induce caspase-dependent apoptotic cell death characterized by concentration- and time-dependent mitochondrial membrane depolarization, activation of caspases-3 and -7, sub-G0/G1 DNA formation
"highlight2" >Apoptosis↑,
"highlight2" >MMP↓,
"highlight2" >TumCCA↑,
"highlight2" >eff↑, have led the World Health Organization to recommend the use of ART-based combination therapies to all countries experiencing resistance to conventional monotherapies.
"highlight2" >eff↑, The most sensitive cell lines are characterized by their rapid proliferation, often accompanied by a high intracellular iron concentration to sustain continued proliferation

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
"highlight2" >Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
"highlight2" >NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
"highlight2" >HO-1↓,
"highlight2" >PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
"highlight2" >Akt↓,
"highlight2" >TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

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
"highlight2" >Apoptosis↑, The combination of Ara-C and DHA synergistically promoted the apoptosis and differentiation of HL-60 cells
"highlight2" >Diff↑,
"highlight2" >ROS↓, Mechanistically, synergistic cytotoxic effects of Ara-C/DHA on HL-60 cells may be mediated by decreasing intracellular ROS levels
"highlight2" >HO-1↓, However, DHA only caused the down-regulation of HO-1, whereas the expression level of nuclear Nrf2 was unaffected.
"highlight2" >NRF2∅,

4991- ART/DHA,  doxoR,    Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy
- in-vivo, Nor, H9c2
"highlight2" >*cardioP↑, In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes.
"highlight2" >*ROS↓,
"highlight2" >*Ferroptosis↓,
"highlight2" >*NRF2↑,
"highlight2" >Keap1↓, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

2578- ART/DHA,  RES,    Synergic effects of artemisinin and resveratrol in cancer cells
- in-vitro, Liver, HepG2 - in-vitro, Cerv, HeLa
"highlight2" >Dose↝, The combination of ART and Res exhibited the strongest anticancer effect at the ratio of 1:2 (ART to Res).
"highlight2" >TumCMig↓, combination of the two drugs also markedly reduced the ability of cell migration
"highlight2" >Apoptosis↑, Apoptosis analysis showed that combination of ART and Res significantly increased the apoptosis and necrosis rather than use singly
"highlight2" >necrosis↑,
"highlight2" >ROS↑, ROS levels were elevated by combining ART with Res.
"highlight2" >eff↑, the data suggested that the IC50 of the combination of ART and Res is lower than that of each drug used alone.

567- ART/DHA,    An Untargeted Proteomics and Systems-based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells
- in-vitro, Lung, BEAS-2B
"highlight2" >NRF2↑, artesunate is Nrf2 regulator
"highlight2" >AP-1↑,
"highlight2" >NFAT↑,

976- ART/DHA,    Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells
- in-vitro, BC, MCF-7
"highlight2" >ERα/ESR1↓, downregulated ERα protein and transcripts without altering expression or activity of ERβ

957- ART/DHA,    Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels
- in-vitro, ESCC, KYSE150 - in-vitro, ESCC, KYSE170
"highlight2" >TumCP↓,
"highlight2" >TumMeta↓,
"highlight2" >Glycolysis↓,
"highlight2" >N-cadherin↓,
"highlight2" >PKM2↓,
"highlight2" >Hif1a↓,

576- ART/DHA,    Profiling of Multiple Targets of Artemisinin Activated by Hemin in Cancer Cell Proteome
- Analysis, NA, NA
"highlight2" >GSTP1/GSTπ↓, IC50 value of 2 μM
"highlight2" >TfR1/CD71↓,

575- ART/DHA,    Dihydroartemisinin initiates ferroptosis in glioblastoma through GPX4 inhibition
- in-vitro, GBM, U87MG
"highlight2" >GPx4↓,
"highlight2" >xCT∅, constant expression of xCT and ACSL4, suggesting GPX4 was a pivotal target for DHA-activated ferroptosis
"highlight2" >ROS↑, lipid ROS levels were increased
"highlight2" >Ferroptosis↑,
"highlight2" >ACSL4∅,

574- ART/DHA,    Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway
"highlight2" >TumCP↓,
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >MMP17↓,
"highlight2" >p‑EGFR↓,
"highlight2" >p‑Akt↓,

573- ART/DHA,    Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model
- vitro+vivo, NA, NA
"highlight2" >p‑p38↓,
"highlight2" >p‑ERK↓,
"highlight2" >p‑CREB↓,
"highlight2" >p‑Chk2↓,
"highlight2" >p‑STAT5↓,
"highlight2" >p‑RSK↓,
"highlight2" >SOCS1↑,
"highlight2" >Apoptosis↑,
"highlight2" >Casp3↑,

572- ART/DHA,    High-throughput screening identifies artesunate as selective inhibitor of cancer stemness: Involvement of mitochondrial metabolism
"highlight2" >CSCs↓,
"highlight2" >mtDam↑, inducing mitochondrial dysfunction.

571- ART/DHA,  TMZ,    Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibition of homologous recombination and senescence
- vitro+vivo, GBM, A172 - vitro+vivo, GBM, U87MG
"highlight2" >HR↓,
"highlight2" >RAD51↓,
"highlight2" >Apoptosis↑,
"highlight2" >necrosis↑,
"highlight2" >ROS↑,
"highlight2" >ChemoSen↑, Enhancement of the antitumor effect of TMZ by co-administration of ART was also observed in a mouse tumor model.

570- ART/DHA,    Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling
- vitro+vivo, NSCLC, A549 - vitro+vivo, NSCLC, H1299
"highlight2" >TumCCA↑, arresting cell cycle in G1 phase.
"highlight2" >CSCs↓,
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >TumCG↓,
"highlight2" >Wnt/(β-catenin)↓, main pathway
"highlight2" >Nanog↓,
"highlight2" >SOX2↓,
"highlight2" >OCT4↓, oct3/4
"highlight2" >N-cadherin↓,
"highlight2" >Vim↓,
"highlight2" >E-cadherin↑,

569- ART/DHA,    Dihydroartemisinin exhibits anti-glioma stem cell activity through inhibiting p-AKT and activating caspase-3
- in-vitro, GBM, NA
"highlight2" >TumCP↓,
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑, cell cycle arrest in the G1 phase
"highlight2" >Casp3↑,
"highlight2" >p‑Akt↓,

568- ART/DHA,    Mechanism-Guided Design and Synthesis of a Mitochondria-Targeting Artemisinin Analogue with Enhanced Anticancer Activity
- in-vitro, NA, MDA-MB-231 - in-vitro, NA, HeLa - in-vitro, NA, SkBr3 - in-vitro, NA, HCT116
"highlight2" >Iron↝, free heme is the main activator

985- ART/DHA,    Artemisinin suppresses aerobic glycolysis in thyroid cancer cells by downregulating HIF-1a, which is increased by the XIST/miR-93/HIF-1a pathway
- in-vitro, Thyroid, TPC-1 - Human, NA, NA
"highlight2" >XIST↓, HIF-1a is highly expressed in TC tissues and is positively correlated with the level of XIST in the serum of patients with TC.
"highlight2" >Hif1a↓,
"highlight2" >Glycolysis↓,
"highlight2" >TumCCA↑, inhibited the cell cycle, and G1 phase cells increased by 17%
"highlight2" >TumMeta↓, 51%

566- ART/DHA,  2DG,    Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells
- in-vitro, Lung, A549 - in-vitro, Lung, PC9
"highlight2" >GlucoseCon↓,
"highlight2" >ATP↓,
"highlight2" >lactateProd↓,
"highlight2" >p‑S6↓,
"highlight2" >mTOR↓,
"highlight2" >GLUT1↓,
"highlight2" >Casp9↑,
"highlight2" >Casp8↑,
"highlight2" >Casp3↑,
"highlight2" >Cyt‑c↑,
"highlight2" >AIF↑,
"highlight2" >ROS↑, generation of ROS is critical for the toxic effects of DHA

565- ART/DHA,    Artesunate as an Anti-Cancer Agent Targets Stat-3 and Favorably Suppresses Hepatocellular Carcinoma
"highlight2" >STAT↓,
"highlight2" >IL6↓,
"highlight2" >pro‑Casp3↝,
"highlight2" >Bcl-xL↝,
"highlight2" >survivin↝,

564- ART/DHA,  Cisplatin,    Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling
- in-vitro, NA, HN30
"highlight2" >JAK2↓,
"highlight2" >STAT3↓,
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >Mcl-1↓,
"highlight2" >Bcl-xL↓,
"highlight2" >cycD1/CCND1↓,
"highlight2" >VEGF↓,
"highlight2" >TumCCA↑, G1 cell cycle arrest in HNSCC
"highlight2" >ChemoSen↑, DHA also synergized with cisplatin in tumor inhibition in HNSCC cells

563- ART/DHA,    Artesunate down-regulates immunosuppression from colorectal cancer Colon26 and RKO cells in vitro by decreasing transforming growth factor β1 and interleukin-10
- in-vitro, Colon, colon26 - in-vitro, CRC, RKO
"highlight2" >TGF-β↓,
"highlight2" >IL10↓,

562- ART/DHA,    Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression
- in-vivo, NA, HeLa
"highlight2" >CD4+↓,
"highlight2" >CD25+↓,
"highlight2" >FoxP3+↓,
"highlight2" >Treg lymp↓,
"highlight2" >PGE2↓,
"highlight2" >FOXP3↓,
"highlight2" >COX2↓,

561- ART/DHA,    Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo
- in-vivo, NA, NA
"highlight2" >TumCG↓,
"highlight2" >CD4+↓,
"highlight2" >CD25+↓,
"highlight2" >FoxP3+↓,
"highlight2" >IL4↑,

560- ART/DHA,    Dihydroartemisinin shift the immune response towards Th1, inhibit the tumor growth in vitro and in vivo
- in-vivo, NA, NA
"highlight2" >IL4↓,
"highlight2" >CD4+↓,
"highlight2" >CD25+↓,
"highlight2" >FoxP3+↓, Foxp3+
"highlight2" >Treg lymp↓,

559- ART/DHA,    Artemisinin and its derivatives: a promising cancer therapy
- Review, NA, NA
"highlight2" >ROS↑, reacts with the iron in cancer cells to produce ROS

558- ART/DHA,    Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer
- Review, NA, NA
"highlight2" >ROS↑,
"highlight2" >oncosis↑, low doses of artesunate induced oncosis-like cell death
"highlight2" >Apoptosis↑, higher doses of art
"highlight2" >LysoPr↑,
"highlight2" >TumAuto↑,
"highlight2" >Wnt/(β-catenin)↑,
"highlight2" >AMP↓,
"highlight2" >NF-kB↓,
"highlight2" >Myc↓,
"highlight2" >CREBBP↓,
"highlight2" >mTOR↓,
"highlight2" >E-cadherin↑,

557- ART/DHA,    Artemisinin and Its Derivatives in Cancer Care
- Review, Var, NA
"highlight2" >*BioAv↓, with High fat and high calorie meals
"highlight2" >*BioAv↑, DHA dihydroartemisinin have improved bioavailability
"highlight2" >Apoptosis↑,
"highlight2" >EGFR↓,
"highlight2" >CD31↓,
"highlight2" >Ki-67↓,
"highlight2" >P53↓,
"highlight2" >TfR1/CD71↑,
"highlight2" >P-gp↓, many artemisinin derivatives act as P-gp inhibitors
"highlight2" >PD-1↝, Caution when used with mmunotherapy (PD1/PDL1 inhibitors)

556- ART/DHA,    Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing
- Review, NA, NA
"highlight2" >IL6↓,
"highlight2" >IL1↓, IL-1β
"highlight2" >TNF-α↓,
"highlight2" >TGF-β↓, TGF-β1
"highlight2" >NF-kB↓,
"highlight2" >MIP2↓,
"highlight2" >PGE2↓,
"highlight2" >NO↓,
"highlight2" >Hif1a↓,
"highlight2" >KDR/FLK-1↓,
"highlight2" >VEGF↓,
"highlight2" >MMP2↓,
"highlight2" >TIMP2↑,
"highlight2" >ITGB1↑,
"highlight2" >NCAM↑,
"highlight2" >p‑ATM↑,
"highlight2" >p‑ATR↑,
"highlight2" >p‑CHK1↑,
"highlight2" >p‑Chk2↑,
"highlight2" >Wnt/(β-catenin)↓,
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >ERK↓, ERK1/2
"highlight2" >cMyc↓,
"highlight2" >mTOR↓,
"highlight2" >survivin↓,
"highlight2" >cMET↓,
"highlight2" >EGFR↓,
"highlight2" >cycD1/CCND1↓,
"highlight2" >cycE1↓,
"highlight2" >CDK4/6↓,
"highlight2" >p16↑,
"highlight2" >p27↑,
"highlight2" >Apoptosis↑,
"highlight2" >TumAuto↑,
"highlight2" >Ferroptosis↑,
"highlight2" >oncosis↑,
"highlight2" >TumCCA↑, G0/G1 into M phase, G0/G1 into S phase, G1 and G2/M
"highlight2" >ROS↑, ovarian cancer cell line model, artesunate induced oxidative stress, DNA double-strand breaks (DSBs) and downregulation of RAD51 foci
"highlight2" >DNAdam↑,
"highlight2" >RAD51↓,
"highlight2" >HR↓,

1026- ART/DHA,    Artemisinin improves the efficiency of anti-PD-L1 therapy in T-cell lymphoma
"highlight2" >Ferroptosis↑,
"highlight2" >ROS↑,
"highlight2" >ERK↓,
"highlight2" >PD-L1↓, combination therapy with artemisinin greatly improved the anti-lymphoma effciency of anti-PD-L1 monoclonal antibody.

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
"highlight2" >eff↑, Our results indicated that artesunate and allicin in combination exert synergistic effects on osteosarcoma cell proliferation and apoptosis.
"highlight2" >tumCV↓,
"highlight2" >Casp3↑, apoptotic rate was significantly increased through caspase-3/9 expression and activity enhancement
"highlight2" >Casp9↑,
"highlight2" >Apoptosis↑,
"highlight2" >TumCG↓, Combination suppresses in vivo tumor growth

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
"highlight2" >ChemoSen↑, Surprisingly, AS synergistically enhanced the cytotoxic effect of DTX by inducing apoptosis in H23 cells through the caspase-dependent pathway, whereas selectively increased necrotic cell population in A549 cells,
"highlight2" >GPx4↓, ollowing the decline in GPX4 level and reactive oxygen species (ROS) activation with the highest rate in the combination treatment group
"highlight2" >ROS↑,
"highlight2" >Ferroptosis↑, predominant contribution of ferroptosis.
"highlight2" >eff↑, Our study demonstrated that AS can be a promising chemosensitizer with the combination of conventional chemotherapeutic agent DTX for NSCLC

2574- ART/DHA,    Artemisinin: A Promising Adjunct for Cancer Therapy
- Review, Var, NA
"highlight2" >selectivity↑, the high levels of iron intake constitute artemisinin as a targeted therapy for cancer and make cancer cells more susceptible to the cytotoxic effects of the compound
"highlight2" >eff↑, a recent study conducted by Lin Qingsong et al. found that the addition of aminolevulinic acid (ALA) enhances the anticancer properties of artemisinin against colorectal cancer cell lines

2573- ART/DHA,    Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells
- in-vitro, CRC, HCT116
"highlight2" >eff↑, Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells

2572- ART/DHA,  SRF,    Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax
- in-vitro, AML, NA
"highlight2" >CHOP↑, Artemisinins increased CHOP, decreased MCL1,
"highlight2" >Mcl-1↓,
"highlight2" >ChemoSen↑, synergized with BCL2 inhibitors and SOR against human acute leukemia cells in vitro.
"highlight2" >selectivity↑, The SAV combination potently inhibited leukemia cell growth but spared normal HSPCs

2571- ART/DHA,    Cancer combination therapies with artemisinin-type drugs
- Review, Var, NA
"highlight2" >AntiTum↑, We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo.
"highlight2" >ChemoSen↑, Indeed, additive to synergistic interactions of ARS, DHA, or ART have been observed in combination with standard anticancer drugs towards tumor cell lines of diverse origin
"highlight2" >hepatoP↝, In a large meta-analysis with 8000 patients, hepatotoxicity occurred in 0.9% of the patients

2570- ART/DHA,    Discovery, mechanisms of action and combination therapy of artemisinin
- Review, Nor, NA
"highlight2" >*BioAv↓, Because the parent drug of artemisinin is poorly soluble in water or oil, the carbonyl group of artemisinin was reduced to obtain DHA
"highlight2" >*Half-Life↓, artemisinins also have a very short elimination half-life (∼1 h)
"highlight2" >*toxicity↓, Artemisinin and its derivatives are generally safe and well-tolerated.
"highlight2" >*ROS↑, Artemisinins are considered prodrugs that are activated to generate carbon-centered free radicals or reactive oxygen species (ROS).
"highlight2" >GSH↓, earlier studies suggest that artemisinins modulate parasite oxidative stress and reduce the levels of antioxidants and glutathione (GSH) in the parasite
"highlight2" >selectivity↑, Many publications corroborate the essence of iron-dependent bioactivation

2569- ART/DHA,    A semiphysiological pharmacokinetic model for artemisinin in healthy subjects incorporating autoinduction of metabolism and saturable first-pass hepatic extraction
- Human, Nor, NA
"highlight2" >*Half-Life↝, Artemisinin was found to induce its own metabolism with a mean induction time of 1.9 h, whereas the enzyme elimination half-life was estimated to 37.9 h.
"highlight2" >BioAv↝, Artemisinin produces a rapid onset of enzyme induction, resulting in a decrease in its own bioavailability over time.
"highlight2" >*Half-Life↓, Plasma artemisinin concentrations reach a peak within 2–3 h after oral intake and decline with a short half-life of 1.5–2 h
"highlight2" >BioAv↑, Artemisinin is believed to pass through the gut membrane relatively easily [3, 4], although high oral clearance values are indicative of high first-pass metabolism of the compound, resulting in low bioavailability
"highlight2" >*Dose↝, either a daily single dose of 500 mg oral artemisinin for 5 days, or single oral doses of 100/100/250/250/500 mg on each of the first 5 days.

2324- ART/DHA,    Research Progress of Warburg Effect in Hepatocellular Carcinoma
- Review, Var, NA
"highlight2" >PKM2↓, DHA effectively suppressed aerobic glycolysis and ESCC progression by downregulating PKM2 expression in esophageal squamous cell carcinoma (ESCC) and ESCC cells
"highlight2" >GLUT1↓, DHA inhibited leukemia cell K562 proliferation by suppressing GLUT1 and PKM2 levels, thereby regulating glucose uptake and inhibiting aerobic glycolysis
"highlight2" >Glycolysis↓,
"highlight2" >Akt↓, In LNCaP cells, DHA reduced Akt/mTOR and HIF-1α activity, leading to decreased expression of GLUT1, HK2, PKM2, and LDH and subsequent inhibition of aerobic glycolysis
"highlight2" >mTOR↓,
"highlight2" >Hif1a↓,
"highlight2" >HK2↓,
"highlight2" >LDH↓,
"highlight2" >NF-kB↓, DHA was also found to inhibit the NF-κB signaling pathway to prevent GLUT1 translocation to the plasma membrane, thereby inhibiting the progression of non-small-cell lung cancer (NSCLC) cells via targeting glucose metabolism

2323- ART/DHA,    Dihydroartemisinin represses esophageal cancer glycolysis by down-regulating pyruvate kinase M2
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706
"highlight2" >PKM2↓, DHA treatment cells, PKM2 was down-regulated and lactate product and glucose uptake were inhibited.
"highlight2" >lactateProd↓,
"highlight2" >GlucoseCon↓,
"highlight2" >cycD1/CCND1↓, DHA treatment resulted in the down-regulation of the expression of PKM2, cyclin D1, Bcl-2, matrix metalloproteinase-2 (MMP2), vascular endothelial growth factor A (VEGF-A) and the up-regulation of caspase 3, cleaved-PARP and Bax
"highlight2" >Bcl-2↓,
"highlight2" >MMP2↓,
"highlight2" >VEGF↓,
"highlight2" >Casp3↑,
"highlight2" >cl‑PARP↑,
"highlight2" >BAX↑,
"highlight2" >DNAdam↑, The specific mechanism of DHA towards cancer cells include inducing DNA damage and repair (Li et al., 2008), oxidative stress response by reactive oxygen species
"highlight2" >ROS↑,

2322- ART/DHA,    Dihydroartemisinin Regulates Self-Renewal of Human Melanoma-Initiating Cells by Targeting PKM2/LDHARelated Glycolysis
- in-vitro, Melanoma, NA
"highlight2" >TumCP↓, DHA inhibits the proliferation of melanoma cells and blocks the cell cycle process.
"highlight2" >PKM2↓, DHA reduces ATP production and downregulate PKM2 and LDHA activities without regulating the expression of the PKM2 and LDHA proteins in melanoma cells
"highlight2" >LDHA↓,
"highlight2" >Glycolysis↓, downregulates glucose metabolism in melanoma cells.

2321- ART/DHA,    Dihydroartemisinin mediating PKM2-caspase-8/3-GSDME axis for pyroptosis in esophageal squamous cell carcinoma
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706
"highlight2" >Pyro↑, DHA treatment to ESCC, we found that some dying cells exhibited the characteristic morphology of pyroptosis, such as blowing large bubbles from the cell membrane,
"highlight2" >PKM2↓, accompanied by downregulation of pyruvate kinase isoform M2 (PKM2),
"highlight2" >Casp8↑, activation of caspase-8/3, and production of GSDME-NT
"highlight2" >Casp3↑,
"highlight2" >Warburg↓, previous studies, we demonstrated that DHA has anti-esophageal cancer effects by blocking the cell cycle in G0/G1 phase, inducing apoptosis, regulating the NF-κB/HIF-1α/VEGF pathway ... and downregulating the expression of PKM2 to inhibit the Warburg
"highlight2" >TumCCA↑,
"highlight2" >Apoptosis↑,

2320- ART/DHA,    Dihydroartemisinin Inhibits the Proliferation of Leukemia Cells K562 by Suppressing PKM2 and GLUT1 Mediated Aerobic Glycolysis
- in-vitro, AML, K562 - in-vitro, Liver, HepG2
"highlight2" >Glycolysis↓, DHA prevented cell proliferation in K562 cells through inhibiting aerobic glycolysis.
"highlight2" >GlucoseCon↓, Lactate product and glucose uptake were inhibited after DHA treatment.
"highlight2" >lactateProd↓,
"highlight2" >GLUT1↓, DHA modulates glucose uptake through downregulating glucose transporter 1 (GLUT1) in both gene and protein levels.
"highlight2" >PKM2↓, DHA treatment, decreased expression of PKM2 was confirmed in situ.
"highlight2" >ECAR↓, ECAR parameters including the glycolytic activity and capacity decreased in a concentration-dependent manner in K562 cells following DHA administration
"highlight2" >LDHA↓, DHA treatment downregulated the relative expression of GLUT1, PKM2, LDH-A and c-Myc
"highlight2" >cMyc↓,
"highlight2" >other↝, The relative changes of PDK1, P53, HIF-1α, HK2, and PFK1 expression were modest, with most genes being altered by less than 2-fold

1148- ART/DHA,    Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages
- in-vitro, AML, THP1
"highlight2" >MMP9↓,
"highlight2" >EMMPRIN↓,
"highlight2" >p‑PKCδ↓, artemisinin (20-80 μg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation
"highlight2" >p‑JNK↓,
"highlight2" >p‑p38↓,
"highlight2" >p‑ERK↓,

1147- ART/DHA,    Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1
- vitro+vivo, Ovarian, HO-8910 - vitro+vivo, Nor, HUVECs
"highlight2" >angioG↓, 0.5 approximately 50 micromol/l
"highlight2" >TumCG↓,
"highlight2" >VEGF↓, remarkably lowered VEGF expression on tumor cells
"highlight2" >KDR/FLK-1↓,
"highlight2" >*toxicity↓, known low toxicity of ART

1099- ART/DHA,    Dihydroartemisinin inhibits IL-6-induced epithelial–mesenchymal transition in laryngeal squamous cell carcinoma via the miR-130b-3p/STAT3/β-catenin signaling pathway
- in-vitro, NA, NA
"highlight2" >EMT↓,
"highlight2" >TumCI↓,
"highlight2" >STAT3↓,
"highlight2" >β-catenin/ZEB1↓,

1079- ART/DHA,    Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2
- in-vitro, GC, BGC-823 - in-vitro, GC, HGC27 - in-vitro, GC, MGC803
"highlight2" >TumCP↓,
"highlight2" >Apoptosis↑,
"highlight2" >COX2↓,
"highlight2" >BAX↑,
"highlight2" >Bcl-2↓,
"highlight2" >Casp3↑,
"highlight2" >Casp9↑,
"highlight2" >MMP↓,

1076- ART/DHA,    The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer
- Review, NA, NA
"highlight2" >Ferroptosis↑,
"highlight2" >ROS↑, interaction between heme-derived iron and ART will result in the production of ROS
"highlight2" >ER Stress↑,
"highlight2" >i-Iron↓, DHA can cause intracellular iron depletion in a time- and dose-dependent manner
"highlight2" >TumAuto↑,
"highlight2" >AMPK↑,
"highlight2" >mTOR↑,
"highlight2" >P70S6K↑,
"highlight2" >Fenton↑,
"highlight2" >lipid-P↑,
"highlight2" >ROS↑,
"highlight2" >ChemoSen↑, combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.
"highlight2" >NRF2↑, Liu et al. discovered that ART covalently targets Keap1 at Cys151 to activate the Nrf2-dependent pathway [94
"highlight2" >NRF2↓, inhibition of Nrf2-related gene expression accelerated erastin and sorafenib-induced ferroptosis [45]. More importantly, an accumulating body of research suggests that ART may induce ferroptosis in cancer cells by regulating the above molecules.

1075- ART/DHA,    Artemisinin derivatives inactivate cancer-associated fibroblasts through suppressing TGF-β signaling in breast cancer
- in-vitro, Nor, L929
"highlight2" >*TGF-β↓,

1074- ART/DHA,    Artemisinin attenuates lipopolysaccharide-stimulated proinflammatory responses by inhibiting NF-κB pathway in microglia cells
- in-vitro, Nor, BV2
"highlight2" >*TNF-α↓,
"highlight2" >*IL6↓,
"highlight2" >*MCP1↓,
"highlight2" >*NO↓,
"highlight2" >*iNOS↓,
"highlight2" >*IκB↑,

2577- ART/DHA,    Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives
- Review, Var, NA
"highlight2" >eff↑, Artemisinin-transferrin conjugate has been shown to be more potent than artemisinin in killing cancer cells
"highlight2" >TumCCA↑, ART has been shown to act on the G 1 phase , and DHA and ARS on the G2/M phase arrest
"highlight2" >BioAv↑, Artemetherâ's solubility has been increased by 3- to 15-fold using pegylated lysine-based copolymeric den- dritic micelles (5-25 nm, loading 0.5-1 g/g) with prolonged release of up to 1-2 days in vitro
"highlight2" >eff↑, ART crystals have been encapsulated with chitosan, gelatin, and alginate (766 nm) with a 90% encapsulation efficiency and improved hydrophilicity
"highlight2" >ChemoSen↑, Combining artemisinins with chemotherapy in nano drug delivery systems can improve efficacy through higher com- bination index

2579- CUR,  ART/DHA,    Curcumin-Artemisinin Combination Therapy for Malaria
- in-vivo, NA, NA
"highlight2" >OS↑, oral regimen of curcumin with a single injection of α,β-arteether at 750 μg or 1.5 mg per infected mouse led to complete protection of animals against recrudescence and 100% survival
"highlight2" >toxicity↓, Curcumin is tolerated at very high doses, and as much as 8 g/day has been given for 3 months to cancer patients on trial without toxic side effects (1)


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 94

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned ⓘ

CYP24A1↓, 1,  

Redox & Oxidative Stress ⓘ

Fenton↑, 3,   Ferroptosis↑, 17,   GPx4↓, 6,   GPx4↑, 1,   GSH↓, 7,   GSH↝, 1,   GSTP1/GSTπ↓, 1,   HO-1↓, 2,   Iron↓, 1,   Iron↑, 6,   Iron↝, 1,   i-Iron↓, 1,   Keap1↓, 1,   lipid-P↑, 7,   MDA↑, 1,   Mets↑, 1,   NRF2↓, 2,   NRF2↑, 5,   NRF2∅, 1,   ROS↓, 1,   ROS↑, 31,   ROS∅, 1,   xCT∅, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 4,   NCOA4↑, 1,   NCOA4↝, 1,   Tf↓, 1,   Tf↑, 1,   TfR1/CD71↓, 2,   TfR1/CD71↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   AIF↑, 1,   ATP↓, 1,   CDC25↓, 1,   MMP↓, 5,   mtDam↑, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4∅, 1,   AMP↓, 1,   AMPK↑, 3,   cMyc↓, 4,   p‑CREB↓, 1,   ECAR↓, 1,   FAO↑, 1,   GlucoseCon↓, 4,   Glycolysis↓, 6,   HK2↓, 1,   lactateProd↓, 4,   LDH↓, 1,   LDHA↓, 2,   NADPH↓, 1,   PKM2↓, 7,   PPARγ↑, 1,   p‑S6↓, 1,   SCD1↓, 1,   SIRT1↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 5,   p‑Akt↓, 2,   Apoptosis↓, 1,   Apoptosis↑, 18,   BAX↑, 6,   Bcl-2↓, 4,   Bcl-2↑, 1,   Bcl-xL↓, 1,   Bcl-xL↝, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↓, 1,   Casp3↑, 10,   cl‑Casp3↑, 1,   pro‑Casp3↝, 1,   Casp8↑, 3,   Casp9↑, 6,   p‑Chk2↓, 1,   p‑Chk2↑, 1,   Cyt‑c↑, 5,   DR5↑, 1,   FADD↑, 1,   Fas↑, 1,   Ferroptosis↑, 17,   JNK↓, 1,   JNK↑, 1,   p‑JNK↓, 1,   Mcl-1↓, 3,   MDM2↓, 1,   MOMP↑, 2,   Myc↓, 1,   necrosis↑, 2,   oncosis↑, 2,   p27↑, 2,   p38↑, 1,   p‑p38↓, 2,   Pyro↑, 1,   p‑RSK↓, 1,   survivin↓, 3,   survivin↝, 1,   YAP/TEAD↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   other↓, 2,   other↝, 2,   tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   eIF2α↑, 2,   ER Stress↓, 1,   ER Stress↑, 6,   GRP78/BiP↑, 5,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↑, 1,   PERK↑, 2,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 2,   p62↓, 1,   TumAuto↑, 11,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑ATR↑, 1,   p‑CHK1↑, 1,   DNAdam↑, 6,   HR↓, 2,   p16↑, 2,   P53↓, 1,   P53↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   RAD51↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↑, 1,   CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 3,   CDK4↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 2,   cycE1↓, 1,   E2Fs↓, 1,   P21↑, 1,   TumCCA↑, 15,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   cMET↓, 1,   CREBBP↓, 1,   CSCs↓, 3,   CSCs↑, 1,   Diff↑, 2,   EMT↓, 3,   ERK↓, 3,   p‑ERK↓, 2,   HH↓, 1,   IGF-1R↓, 1,   mTOR↓, 5,   mTOR↑, 2,   mTORC1↓, 1,   Nanog↓, 2,   OCT4↓, 2,   P70S6K↑, 1,   PI3K↓, 3,   SOX2↓, 1,   STAT↓, 1,   STAT3↓, 4,   p‑STAT3↓, 1,   p‑STAT5↓, 1,   TOP2↓, 1,   TRF2↓, 1,   TumCG↓, 8,   Wnt↓, 1,   Wnt/(β-catenin)↓, 2,   Wnt/(β-catenin)↑, 1,  

Migration ⓘ

AP-1↓, 1,   AP-1↑, 1,   AXL↓, 1,   Ca+2↑, 2,   CAFs/TAFs↓, 1,   CD31↓, 1,   Cdc42↑, 1,   CDK4/6↓, 1,   E-cadherin↑, 4,   EMMPRIN↓, 1,   ITGB1↑, 1,   Ki-67↓, 2,   LysoPr↑, 1,   MMP17↓, 1,   MMP2↓, 5,   MMP7↓, 1,   MMP9↓, 6,   N-cadherin↓, 3,   NCAM↑, 1,   NFAT↑, 1,   PKCδ↓, 1,   p‑PKCδ↓, 1,   Slug↓, 1,   Snail?, 1,   TGF-β↓, 3,   TIMP2↑, 2,   Treg lymp↓, 2,   TumCI↓, 4,   TumCMig↓, 5,   TumCP↓, 11,   TumCP↑, 1,   TumMeta↓, 5,   Twist↓, 1,   uPA↓, 3,   Vim↓, 2,   Zeb1↓, 1,   ZEB2↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 8,   ATF4↑, 3,   EGFR↓, 2,   p‑EGFR↓, 1,   EPR↑, 1,   Hif1a↓, 5,   KDR/FLK-1↓, 2,   NO↓, 1,   VEGF↓, 7,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 4,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD25+↓, 3,   CD4+↓, 3,   COX2↓, 6,   FOXP3↓, 1,   FoxP3+↓, 3,   IL1↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL4↓, 2,   IL4↑, 1,   IL6↓, 2,   IL8↓, 2,   JAK2↓, 1,   M2 MC↓, 1,   MIP2↓, 1,   NF-kB↓, 7,   PD-1↝, 1,   PD-L1↓, 1,   PGE2↓, 2,   SOCS1↑, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,   CDK6↑, 1,   ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 3,   BioAv↝, 2,   ChemoSen↑, 13,   Dose↝, 3,   eff↓, 7,   eff↑, 28,   eff↝, 2,   Half-Life?, 1,   Half-Life↓, 2,   RadioS↑, 1,   selectivity↑, 7,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   p‑EGFR↓, 1,   ERα/ESR1↓, 1,   Ferritin↓, 4,   IL6↓, 2,   Ki-67↓, 2,   LDH↓, 1,   Myc↓, 1,   PD-L1↓, 1,   XIST↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 5,   AntiTum↑, 2,   hepatoP↝, 1,   OS↑, 1,   toxicity↓, 2,   toxicity↑, 1,   TumVol↓, 1,  
Total Targets: 272

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↓, 1,   Catalase↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   GSH↓, 1,   GSH∅, 1,   HO-1↑, 1,   MDA↑, 1,   NRF2↑, 2,   ROS↓, 5,   ROS↑, 1,   SOD↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Akt↑, 1,   Casp3↓, 1,   Casp9↓, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   iNOS↓, 2,   p‑p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   p‑ERK↓, 1,  

Migration ⓘ

ROCK1↓, 1,   TGF-β↓, 1,   TGF-β↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↓, 4,   Inflam↓, 6,   IκB↑, 1,   MCP1↓, 2,   MIP2↓, 1,   MyD88↓, 1,   NF-kB↓, 4,   NF-kB↑, 1,   TLR4↓, 2,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   Dose↝, 1,   Half-Life↓, 2,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

IL6↓, 4,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 2,   memory↑, 2,   neuroP↑, 3,   toxicity↓, 2,  
Total Targets: 52

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:34  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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