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2327- 2DG,    2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents
- Review, Var, NA
Glycolysis↓, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death
HK2↓,
mt-ROS↑, 2-DG-mediated glucose deprivation stimulates reactive oxygen species (ROS) production in mitochondria, also leading to AMPK activation and autophagy stimulation.
AMPK↑,
PPP↓, 2-DG has been shown to block the pentose phosphate shunt
NADPH↓, Decreased levels of NADPH correlate with reduced glutathione levels, one of the major cellular antioxidants.
GSH↓,
Bax:Bcl2↑, Valera et al. also observed that in bladder cancer cells, 2-DG treatment modulates the Bcl-2/Bax protein ratio, driving apoptosis induction
Apoptosis↑,
RadioS↑, 2-DG radiosensitization results from its effect on thiol metabolism
eff↓, (NAC) treatment, downregulated glutamate cysteine ligase activity, or overexpression of ROS scavenging enzymes
Half-Life↓, its plasma half-life was only 48 min [117]) make 2-DG a rather poor drug candidate
other↝, Adverse effects of 2-DG administration in humans include fatigue, sweating, dizziness, and nausea, mimicking the symptoms of hypoglycemia
eff↓, Moreover, 2-DG has to be used at relatively high concentrations (≥5 mmol/L) in order to compete with blood glucose

5272- 3BP,    The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

5261- 3BP,    The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH
- in-vitro, BC, NA
eff↑, Transport of the anti-cancer agent 3-bromopyruvate (3BP) in breast cancer cells is mediated by monocarboxylate transporter (MCT)-1 activated by glycosylated chaperone cluster of differentiation (CD) 147. T
eff↓, The extracellular acidic pH increases the affinity for 3BP uptake enhancing its selective cytotoxic effect in tumour cells.

3972- ACNs,    Recent Research on the Health Benefits of Blueberries and Their Anthocyanins
- Review, AD, NA - Review, Park, NA
*cardioP↑, Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection.
*neuroP↑,
*Inflam↓, Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function
*antiOx↓,
*GutMicro↑, Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health
*Half-Life↑, However, >50% of the 13C still remained in the body after 48 h
*LDL↓, controlled study of 58 diabetic patients, blueberry intake led to a decline in LDL cholesterol, triglycerides, and adiponectin and an increase in HDL cholesterol
*adiP↓,
*HDL↑,
*CRP↓, reduction was documented in inflammatory markers, including serum high-sensitivity C-reactive protein, soluble vascular adhesion molecule-1, and plasma IL-1β
*IL1β↓,
*Risk↓, lower Parkinson disease risk was associated with the highest quintile of anthocyanin (RR: 0.76) and berry (RR: 0.77) intake
*Risk↓, Nurse's Health Study, greater intake of blueberries and strawberries was associated with slower rates of cognitive decline in older adults, with an estimated delay in decline of about 2.5 y
*cognitive↑, Cognitive performance in elderly adults improved after 12 wk of daily intake of blueberry (94) or Concord grape (95) juice.
*memory↑, Better task switching and reduced interference in memory was found in healthy older adults after 90 d of blueberry supplementation
*other↑, After 12 wk of blueberry consumption, greater brain activity was detected using magnetic resonance imaging in healthy older adults during a cognitive challenge.
*BOLD↑, Similarly, during a memory test, regional blood oxygen level-dependent activity detected by MRI (99) was enhanced in the subjects taking blueberry, but not in those taking placebo.
*NO↓, 50–200 mg/d bilberry showed a dose-dependent decrease in neurotoxic NO and malondialdehyde, combined with an increase in neuroprotective antioxidant capacity due to glutathione, vitamin C, superoxide dismutase, and glutathione peroxidase
*MDA↓,
*GSH↑,
*VitC↑,
*SOD↑,
*GPx↑,
*eff↓, The percentage loss of blueberry anthocyanins during −18°C storage was 12% after 10 mo of storage
*eff↓, Freeze-dried blueberry powder loses anthocyanins in a temperature-dependent manner with a half-life of 139, 39, and 12 d when stored at 25, 42, and 60°C, respectively
*eff↓, Blueberries are low in ascorbic acid and high in anthocyanins (187), and notably anthocyanins are readily degraded by ascorbic acid
*eff↝, Shelf-stable blueberry products like jam (196), juice (197), and extracts (198) can lose polyphenolic compounds when stored at ambient temperature whereas refrigeration mitigates losses.
*Risk↓, It can be safely stated that daily moderate intake (50 mg anthocyanins, one-third cup of blueberries) can mitigate the risk of diseases and conditions of major socioeconomic importance in the Western world.

5459- AF,    Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells
- in-vitro, Ovarian, NA
ROS↑, AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer.
TrxR↓, The primary mechanism of action of auranofin is to act as a pro-oxidative agent, increasing the production of reactive oxygen species (ROS) as a consequence of inhibiting the thioredoxin reductase (TrxR) anti-oxidant system
MMP↓, triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis.
Apoptosis↑,
eff↓, Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC).
Casp3↑, lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage
Casp7↑,
DNAdam↑,
eff↑, Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH.
GSH↓,
angioG↓, Additionally, auranofin has been shown to inhibit angiogenesis
ChemoSen↑, In this study, we identified the mechanisms of cytotoxicity induced by auranofin in HGSOC cells that have different clinical sensitivities to platinum.
cl‑PARP↑, the cleavage of poly-ADP ribose polymerase (PARP), and the polyubiquitination of proteins
eff↑, synergistic lethal interaction between auranofin and a second pro-oxidant agent, the glutathione (GSH) inhibitor, L-buthionine sulfoximine (L-BSO);

5460- AF,    Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species
- vitro+vivo, Var, 4T1
RadioS↑, AF at 3–10 μM is a potent radiosensitizer in vitro
ROS↑, . The first one is linked to an oxidative stress, as scavenging of reactive oxygen species (ROS)
eff↓, N-acetyl cysteine counteracted radiosensitization. (NAC)
mt-OCR↓, We also observed a decrease in mitochondrial oxygen consumption with spared oxygen acting as a radiosensitizer under hypoxic conditions.
DNAdam↑, Overall, radiosensitization was accompanied by ROS overproduction, mitochondrial dysfunction, DNA damage and apoptosis
Apoptosis↑,
TrxR↓, targeting thioredoxin reductase (TrxR)
eff↑, a simultaneous disruption of the thioredoxin and glutathione systems by the combination of AF and buthionine sulfoximine was shown to significantly improve tumor radioresponse.

5472- AF,    Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion
- in-vitro, Cerv, HeLa
TrxR↓, Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti‑cancer drug
AntiCan↑,
TumCG↓, Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h.
Apoptosis↑, This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP‑ribose) polymerase and loss of mitochondrial membrane potential.
necrosis↑,
cl‑PARP↑,
MMP↓,
ROS↑, With respect to the levels of ROS and GSH, Au increased intracellular O2•- in the HeLa cells and induced GSH depletion.
GSH↓,
eff↓, The antioxidant, N‑acetyl cysteine, not only attenuated apoptosis and necrosis in the Au‑treated HeLa cells, but also decreased the levels of O2•- and GSH depletion in the cells.

5468- AF,    The gold complex auranofin: new perspectives for cancer therapy
- Review, Var, NA
TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

5236- AgNPs,    Adaptive regulations of Nrf2 alleviates silver nanoparticles-induced oxidative stress-related liver cells injury
- in-vitro, Liver, HepG2 - in-vitro, Nor, L02
tumCV↓, AgNPs induced a concentration-dependent decline in HepG2 and L02 cells viability.
ROS↑, • AgNPs induced ROS increase and apoptosis in HepG2 and L02 cells.
*ROS↑,
DNAdam↑, AgNPs induced DNA damage, autophagy and cell cycle arrest in HepG2 and L02 cells.
*DNAdam↑,
eff↓, N-acetylcysteine (NAC)alleviated AgNPs-induced cytotoxicity in HepG2 and L02 cells.
selectivity↑, Interestingly, HepG2 cells were more sensitive to AgNPs than L02 cells, and this may be related to the different ROS generation and responses to AgNPs by cancer cells and normal cells.

5237- AgNPs,    Nrf2 Activation Mitigates Silver Nanoparticle-Induced Ferroptosis in Hepatocytes
- in-vitro, Liver, HepG2
Ferroptosis↑, we provide evidence that AgNPs trigger ferroptosis in both mouse hepatocytes and HepG2 cells
p62↑, AgNPs increased p62 expression, which in turn stabilized Nrf2 by suppressing its interaction with Keap1.
NRF2↝,
eff↓, Upon activation, Nrf2 enhances the transcription of key antioxidant enzymes, including NQO1 and HO-1, thereby alleviating ferroptosis.

1907- AgNPs,  GoldNP,  Cu,    In vitro antitumour activity of water soluble Cu(I), Ag(I) and Au(I) complexes supported by hydrophilic alkyl phosphine ligands
- in-vitro, Lung, A549 - in-vitro, BC, MCF-7 - in-vitro, Melanoma, A375 - in-vitro, Colon, HCT15 - in-vitro, Cerv, HeLa
TrxR↓, In particular, [Au(PTA)4]PF6 was able to decrease by 50% TrxR activity at 4.2 nM
eff↓, C 50 value calculated for [Ag(PTA) 4]PF6 was 10.3 nM.
eff↓, Conversely, [Cu(PTA)4]PF6 was found to be much less effective in inhibiting this cytosolic selenoenzyme, with an IC50 value of 89.5 nM, roughly from 9 to 21 times higher than those calculated for silver and gold derivatives,
other∅, To the best of our knowledge, this is the first example of a phosphino silver complex acting as TrxR inhibitor.

1906- AgNPs,  GoldNP,  Cu,    Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
- Review, Var, NA
TrxR↓, 183(Au) was able to decrease TrxR activity by 50% at 4.20 nM
eff↓, IC 50 value calculated for 184(Ag) was 10.30 nM
eff↓, Conversely, 185(Cu) was found to be much less effective in inhibiting TrxR activity, with an IC 50 value of 89.50 nM

4400- AgNPs,  Rad,    Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells
- in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549 - in-vivo, BC, MDA-MB-231
ROS↑, AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death.
DNAdam↑,
selectivity↑, We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages.
TumCG↓, reduce TNBC growth and improve radiation therapy.
RadioS↑,
Dose↝, s 23±14 nm: particles were diluted to 40 μg/mL. 25 μg/mL AgNP dilution for 24 hours. zeta potential of AgNPs in water at pH 7 was approximately −36 mV, indicating good colloidal stability.
selectivity↑, Depending on AgNP dose, all three TNBC cell lines were 5- to 10-fold more sensitive to AgNP exposure than the nontumorigenic breast cells.
other↝, this study demonstrate that the cytotoxicity was dependent on exposure of cells to intact AgNPs and not due to Ag+ ions
eff↓, toxicity of AgNPs was significantly reduced in MDA-MB-231, MCF-7, and MCF-10A cells following pretreatment with GSH
eff↑, Selective depletion of GSH by BSO resulted in increased AgNP toxicity in all cell lines.
γH2AX↑, AgNPs significantly increased γH2AX in these cells compared to radiation alone.
Dose↓, Strikingly, an AgNP dose of as little as 1 μg/mL resulted in a dose enhancement of IR treatment (approximately 2-fold at the 2 Gy dose) f
eff↑, Moreover, intratumoral injection of AgNPs with or without radiation treatment can inhibit the growth of TNBC xenografts in mice

4381- AgNPs,    Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells
- in-vitro, Liver, HepG2
eff↓, toxicity of AgNPs was prevented by use of the antioxidant N-acetylcysteine, and AgNP-induced DNA damage was also prevented by N-acetylcysteine.
ROS↑, AgNP cytotoxicity is primarily the result of oxidative stress and is independent of the toxicity of Ag+ ions.
other↑, Ag exposure is associated with specific clinical symptoms, such as argyria, which causes an irreversible gray coloration of the skin

4380- AgNPs,    Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways
- in-vitro, Lung, A549
ROS↑, AgNPs caused ROS formation in the cells
tumCV↓, reduction in their cell viability
MMP↓, and mitochondrial membrane potential (MMP)
TumCCA↑, increase in the proportion of cells in the sub-G1 (apoptosis) population, S phase arrest
PCNA↓, down-regulation of the cell cycle associated proliferating cell nuclear antigen (PCNA) protein
eff↓, Pretreatment of the A549 cells with N-acetyl-cysteine (NAC), an antioxidant, decreased the effects of AgNPs

4375- AgNPs,    The cellular uptake and cytotoxic effect of silver nanoparticles on chronic myeloid leukemia cells
- in-vitro, AML, K562
eff↑, AgNPs were demonstrated to be able to enter K562 cells (a CML cell line) in a dose-dependent manner and locate in endosomes
ROS↑, Reactive oxygen species (ROS) could be generated upon AgNPs exposure and cause cytotoxicity and apoptosis.
Apoptosis↑,
eff↓, alterations caused by AgNPs exposure could be reversed by the addition of Vitamin C (an antioxidant).

4564- AgNPs,  GoldNP,  Cu,  Chemo,  PDT  Cytotoxicity and targeted drug delivery of green synthesized metallic nanoparticles against oral Cancer: A review
- Review, Var, NA
ROS↑, graphical abstract
DNAdam↑, inducing cell death through apoptotic signaling pathways, and inducing excess reactive oxygen species (ROS) in tumor cells, which leads to oxidative damage and increased production of proapoptotic enzymes
TumCCA↑,
eff↑, Metallic nanoparticles, especially those derived from metals, improve the effectiveness of anticancer agents by facilitating targeted delivery and sustained release at tumor sites.
Apoptosis↑,
eff↓, Au NPs are notable for their biocompatibility and are utilized in photothermal therapy to convert light into heat, effectively destroying cancer cells
ChemoSen↑, Magnesium oxide nanoparticles (MgO NPs) induce apoptosis through ROS production and enhance the impact of chemotherapy drugs, synthesized with plant extracts as reducing agents.

346- AgNPs,  RSQ,    Investigating Silver Nanoparticles and Resiquimod as a Local Melanoma Treatment
- in-vivo, Melanoma, SK-MEL-28 - in-vivo, Melanoma, WM35
ROS↑,
Ca+2↝, disrupt mitochondrial homeostasis of Ca2+
Casp3↑, x2-4
Casp8↑, x2-4
Casp9↑, x4-14
CD4+↑,
CD8+↑,
tumCV↓,
eff↓, NAC, an ROS scavenger, could efficiently protect B16.F10 cells from the cytotoxic effects of Ag+ even when exposed to high concentrations of Ag+ (250 μg/ml)
*toxicity↓, non-toxic in mice as evidenced by: 1) no significant change in weights during the study period and 2) no significant increases in the levels of liver enzymes, (ALP), (AST), and ALT

357- AgNPs,    Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells
- in-vitro, Lung, A549 - in-vitro, Lung, L132
mtDam↑,
ROS↑,
Hif1a↑, HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions HIF-1α knockdown enhances hypoxia induced decrease in cell viability
LC3s↑,
p62↑,
eff↓, Hypoxia decreases the effects of anticancer drugs in solid tumor cells through the regulation of HIF-1α

2287- AgNPs,    Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine
- in-vitro, Nor, HUVECs
*TumCP↓, AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability
*ROS↑, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes
*eff↓, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.
*MDA↑, exposure to AgNPs increased MDA levels and decreased GSH levels.
*GSH↓,
*MMP↓, significantly reduced both MMP and ATP levels (Fig. 7) in HUVECs,
*ATP↓,
*LC3II↑, expression levels of LC3-II and p62 were significantly increase
*p62↑,
*Bcl-2↓, the anti-apoptotic protein expression level of Bcl-2 in HUVECs decreased, while the pro-apoptotic protein expression levels of Bax and Caspase-3 increased significantly.
*BAX↑,
*Casp3↑,

2646- AL,    Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress
- in-vitro, Pca, DU145 - in-vitro, Melanoma, RPMI-8226
AntiCan↑, simple homemade ethanol-based garlic extract (GE). We show that GE inhibits growth of several different cancer cells in vitro
eff↓, These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile.
ChemoSen↑, We found that GE enhanced the activities of chemotherapeutics
ER Stress↑, Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER) stress.
tumCV↓, homemade GE was found to reduce the viability of the two multiple myeloma (MM) cell lines, RPMI-8226 and JJN3, as well as the prostate cancer cell line DU145 in a dose-dependent manner,
DNAdam↑, GE alone slightly increased the percentage of tail DNA (% Tail) (representing cumulative levels of abasic sites, as well as single- and double-strand DNA breaks) measured at day one, compared to untreated cells
GSH∅, We could not detect any changes in cellular GSH levels after treatments with GE
HSP70/HSPA5↓, ; however, in support of increased ER stress after GE treatment, we detected an increased pulldown of HSPA5 (BIP), a member of the Hsp70 family
UPR↑, s leading to the accumulation of unfolded proteins in the ER (also known as GRP78)
β-catenin/ZEB1↓, we also found a reduction in the β-catenin leve
ROS↑, In further support for increased ER stress induced by GE, which will lead to elevated ROS-levels and oxidative stress
HO-2↑, we found a significant increase in proteins activated by and important for regulating cellular ROS levels, e.g., OXR1, Txnl1, Hmox2, and Sirt1
SIRT1↑,
GlucoseCon∅, glucose consumption, as well as lactate secretion, were not changed.
lactateProd∅,
chemoP↑, Garlic is reported to reduce cisplatin-induced nephrotoxicity and oxidative stress

1916- AL,    Allicin Bioavailability and Bioequivalence from Garlic Supplements and Garlic Foods
- Review, Nor, NA
*BioAv↝, For enteric tablets, ABB varied from 36–104%
*eff↓, but it was reduced to 22–57% when consumed with a high-protein meal, due to slower gastric emptying.
*BioAv↝, garlic powder capsules gave 26–109%
*BioAv↝, Kwai garlic powder tablets, which have been used in a large number of clinical trials, gave 80% ABB, validating it as representing raw garlic in those trials
*eff↑, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*Half-Life∅, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*eff↑, all brands of normal tablets gave high allicin bioavailability
*eff↑, Hence, both low-protein and high-protein meals would provide a gastric pH ≥ 4.0 for an ample amount of time for the alliinase in disintegrated normal tablets and capsules to convert most of the alliin to allicin in the stomach.
*Dose∅, Three tablets has been the most common dose used in these trials. The N1 tablets in these trials have been consistently standardized to contain 3.9 mg alliin/tablet and to yield 1.8 mg allicin/tablet
*eff↑, The bioavailability of allicin from garlic powder supplements containing alliin and active alliinase can be as high as that from an equivalent amount of crushed raw garlic containing maximum allicin, when consumed with a meal.

235- AL,    Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway
- in-vitro, GBM, U87MG
Apoptosis↑,
Bcl-2↓,
BAX↑,
MAPK↑, mechanisms involved in apoptosis include the mitochondrial pathway, activation of mitogen-activated protein kinases (MAPKs), and caspase cascade and oxidant enzyme system.
p‑ERK↑, In the present study, the level of ERK phosphorylation was increased
ROS↑, ROS are related to allicin-induced apoptosis in the U87MG cells.
eff↓, This study demonstrated that allicin-induced apoptosis was down-regulated by the antioxidant enzyme system

234- AL,    Allicin Induces Anti-human Liver Cancer Cells through the p53 Gene Modulating Apoptosis and Autophagy
- in-vitro, HCC, Hep3B
ROS↑, increased the production of ROS levels at 1, 3, 6 h. I
*toxicity∅, In other study, allicin treatment did not increase the leakage of lactate-dehydrogenase (LDH) of primary rat hepatocytes until 1 mM allicin treated with rat hepatocytes24. For this reason, allicin could be inferred as safe to normal liver cells
MMP↓, Allicin decreased mitochondrial membrane potential
BAX↑,
Bcl-2↓,
AIF↑,
Casp3↑, protein expression levels of caspase-3, -8, -9 increased after allicin treatment
Casp8↑,
Casp9↑,
eff↓, Allicin significantly induced ROS overproduction, whereas NAC pretreatment decreased the ROS induction by allicin exposure in Hep 3B cells
γH2AX↑, significant increase in the expression of γ-H2AX was observed at the initial stages (3, 6 h), but not at the later stages of 12, 24, 48 h
selectivity↑, data suggested that allicin induced apoptosis in p53-deficiency human liver carcinoma cells but caused autophagy in p53-normal function human liver carcinoma cells.
DNA-PK↑, increases production of ROS, triggers DNA damage

3272- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*antiOx↑, LA has long been touted as an antioxidant,
*glucose↑, improve glucose and ascorbate handling,
*eNOS↑, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*NRF2↑,
*MMP9↓,
*VCAM-1↓,
*NF-kB↓,
*cardioP↑, used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits,
*cognitive↑,
*eff↓, The efficiency of LA uptake was also lowered by its administration in food,
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies;
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑, LA markedly increases intracellular glutathione (GSH),
*PKCδ↑, PKCδ, LA activates Erk1/2 [92,93], p38 MAPK [94], PI3 kinase [94], and Akt
*ERK↑,
*p38↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN [95],
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, stimulate GLUT4 translocation
*GLUT1↑, LA-stimulated translocation of GLUT1 and GLUT4.
*Inflam↓, LA as an anti-inflammatory agent

3454- ALA,    Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

281- ALA,    Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation
- in-vitro, Lung, H460
mt-ROS↑, mitochondria are the primary source of ROS production induced by LA and that these ROS are involved in the apoptotic process.
Apoptosis↑,
Casp9↑,
Bcl-2↓,
eff↓, that all the tested antioxidants were able to inhibit apoptosis induced by LA or DHLA indicating that multiple ROS are involved in the apoptotic process.
eff↑, The pro-oxidant role of LA is generally observed under nonoxidative stress conditions, which is also supported by this study
H2O2↑, LA also induced peroxide generation in these cells
Dose↑, 100uM was enough to generate mitochondrial ROS in lung cancer cells

5360- almon,  BEV,    Case report: Almonertinib in combination with bevacizumab for leptomeningeal metastases from epidermal growth factor receptor-mutation non-small cell lung cancer: Case series
- Case Report, NSCLC, NA
BBB↑, Both almonertinib and bevacizumab are capable of crossing the blood–brain barrier with comparable central nervous system effectiveness.
Dose↝, present five cases to further evaluate the effectiveness and tolerability of almonertinib in combination with bevacizumab for patients with EGFRm NSCLC and LM.
eff↓, For the first time, we report that almonertinib plus bevacizumab can not only effectively improve the neurological symptoms caused by LM but also prolong the survival time of patients with limited and controllable side effects, which provided a novel
OS↑,

1440- AMQ,    Lysosomotropism depends on glucose: a chloroquine resistance mechanism
- in-vitro, BC, 4T1
eff↑, Importantly, we found that the related compound, amodiaquine, was more potent than CQ for cell killing and not susceptible to interference from glucose starvation.
Apoptosis↓,
Necroptosis↑,
eff↓, Unexpectedly, further withdrawal of glucose, in the context of serum starvation, fully rescued the effect of CQ
ChemoSen↑, CQ markedly enhanced the sensitivity of 4T1 cells to doxorubicin
eff↓, Inhibition of glycolysis with 2DG also rescued cells from CQ.

1354- And,    Andrographolide induces protective autophagy and targeting DJ-1 triggers reactive oxygen species-induced cell death in pancreatic cancer
- in-vitro, PC, NA - in-vivo, PC, NA
Apoptosis↑,
DJ-1↓, reduction in DJ-1 expression caused by Andro led to ROS accumulation
ROS↑,
TumAuto↑,
TumCCA↑, G2/M phase
TumCP↓,
TumW↓,
eff↓, pro-apoptotic effect of Andro was attenuated when NAC was co-administered

4765- antiOx,  Chemo,    Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity – Exploring the armoury of obscurity
- Review, Var, NA
chemoP↑, Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity
ChemoSen↑, Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients
OS↑,
Dose↑, On the contrary, many integrative practitioner converse uses of antioxidant supplements allowing patients to tolerate possibly higher effective doses of chemotherapy
Risk↓, Among antioxidant users, frequent use of vitamin C and vitamin E was associated with decreased risk of BC recurrence, vitamin E use was associated with decreased risk of all cause mortality
eff↓, but conversely, frequent use of combination carotenoids was associated with increased risk of death from breast cancer and all cause mortality

4746- antiOx,  Chemo,  VitA,RetA,  VitC,  Se  Using Supplements During Chemo: Yes or No?
- Review, Var, NA
eff↓, Taking antioxidants in supplement form (again, remember that antioxidants in food are fine) may actually “protect” cancer cells during treatment.
ChemoSen↓, In other words, antioxidants in pill form have the potential to counteract the effects of chemotherapy or radiation therapy.
RadioS↓,
other↝, Common antioxidant supplements taken by patients include vitamins A, C, and E, carotenoids (such as beta-carotene and lycopene) as well as selenium and Coenzyme Q10.

1536- Api,    Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells
- in-vitro, MM, MSTO-211H - in-vitro, MM, H2452
tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

1564- Api,    Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation
- in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
MDM2↓, downregulation of MDM2 protein
NF-kB↓, Exposure of 22Rv1 cells to 20 μM apigenin caused a decrease in NF-κB/p65 transcriptional activity by 24% at 12 h, which was further decreased to 41% at 24 h
p65↓,
P21↑,
ROS↑, Apigenin at these doses resulted in ROS generation
GSH↓, which was accompanied by rapid glutathione depletion
MMP↓, disruption of mitochondrial membrane potential
Cyt‑c↑, cytosolic release of cytochrome c
Apoptosis↑,
P53↑, accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment
eff↓, All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Casp↑, triggering caspase activation
TumCG↓, in vivo mice
TumVol↓, tumor volume was inhibited by 44 and 59%
TumW↓, wet weight of tumor was decreased by 41 and 53%

1563- Api,  MET,    Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells
- in-vitro, Nor, HDFa - in-vitro, PC, AsPC-1 - in-vitro, PC, MIA PaCa-2 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP - in-vivo, NA, NA
selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

206- Api,    Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress
- in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, Melanoma, A375 - in-vitro, Lung, H2030 - in-vitro, CRC, SW480
Glycolysis↓, glucose consumption, lactate production, and ATP production were all strongly decreased by apigenin
lactateProd↓,
PGK1↓,
ALDOA↓,
GLUT1↓, Apigenin reduces GLUT1 expression levels.
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,
ROS↑, Apigenin causes oxidative stress leading to apoptosis. Because apoptotic signal transduction cascades involving caspase-9, -3 and PARP cleavage can be activated by increased ROS levels
Apoptosis↑,
eff↓, Cancer cells expressing high levels of GLUT1 are resistant to apigenin-induced apoptosis through metabolic compensation of glucose utilization.
NADPH↓, apigenin significantly decreased glucose utilization through suppression of GLUT1 expression, and consequently decreased NADPH production, which led to increased ROS levels.
PPP↓, inhibition of the PPP

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

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

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

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
tumCV↓, DHA significantly reduced cell viability in a dose-dependent manner.
eff↓, Cytotoxicity of DHA was suppressed by N-acetylcysteine (NAC)
Apoptosis↑, induction of cell apoptosis, which were manifested by annexin V-FITC staining, activation of caspase-3
Casp3↑,
ROS↑, DHA also increased ROS generation, cytochrome c release, and loss of mitochondrial transmembrane potential (ΔΨm) in cells.
Cyt‑c↑,
MMP↓,
Bcl-2↓, downregulation of regulatory protein Bcl-2 and upregulation of Bax protein by DHA were also observed
BAX↑,
MOMP↑, Dihydroartemisinin increases mitochondrial permeability of EJ-138 and HTB-9 cells by Collapse of ΔΨm
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

2580- ART/DHA,  VitC,    Effects of Antioxidants and Pro-oxidants on Cytotoxicity of Dihydroartemisinin to Molt-4 Human Leukemia Cells
- in-vitro, AML, NA
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)
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
ROS↑, From our results, we can postulate that ROS generation is causing cell death independently and in combination with DHA
eff↓, Ascorbate can convert ferric iron into ferrous iron (18), the active form that reacts with artemisinin, generating short lived free radicals.
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

1142- Ash,    Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer
- Review, BC, MCF-7 - NA, BC, MDA-MB-231 - NA, Nor, HMEC
Apoptosis↑,
ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
DNAdam↑,
OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
Bcl-2↓,
XIAP↓,
survivin↓,
DR5↑,
IKKα↓,
NF-kB↓,
selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS

1369- Ash,    Withaferin A inhibits cell proliferation of U266B1 and IM-9 human myeloma cells by inducing intrinsic apoptosis
- in-vitro, Melanoma, U266
tumCV↓,
Apoptosis↑,
BAX↑,
Cyt‑c↑,
Bcl-2↓,
cl‑PARP↑,
cl‑Casp3↑,
cl‑Casp9↑,
ROS↑,
eff↓, treatment of the U266B1 and IM-9 with ascorbic acid (antioxidant) could prevent the withaferin A mediated ROS production and the withaferin A induced antiproliferative effects.

1370- Ash,    Withaferin A induces mitochondrial-dependent apoptosis in non-small cell lung cancer cells via generation of reactive oxygen species
- in-vitro, Lung, A549
ROS↑,
eff↓, while the non-carcinoma cells WI-38 and PBMC were unaffected.

1371- Ash,    Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine
- in-vitro, AML, HL-60
ROS↑,
MMP↓,
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
eff↓, N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA.

1373- Ash,    Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells
- in-vitro, Kidney, Caki-1
ER Stress↑,
p‑eIF2α↑,
XBP-1↑,
GRP78/BiP↑,
CHOP↑,
eff↓, Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress.

1357- Ash,    Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vitro, GBM, GL26
TumCP↓,
TumCCA↑, G2/M cell cycle
Akt↓,
mTOR↓,
p70S6↓,
p85S6K↓,
AMPKα↑,
TSC2↑,
HSP70/HSPA5↑,
HO-1↑,
HSF1↓,
Apoptosis↑,
ROS↑, Withaferin A elevates pro-oxidant potential in GBM cells and induces a cellular oxidative stress response
eff↓, Pre-treatment with a thiol-antioxidant protects GBM cells from the anti-proliferative and cytotoxic effects of withaferin A NAC pretreatment was able to completely prevent cell cycle shift to G2/M arrest following 1µM WA treatment at 24h

1360- Ash,  immuno,    Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer
- in-vitro, Lung, H1650 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1361- Ash,  SRF,    Withaferin A, a natural thioredoxin reductase 1 (TrxR1) inhibitor, synergistically enhances the antitumor efficacy of sorafenib through ROS-mediated ER stress and DNA damage in hepatocellular carcinoma cells
- in-vitro, Liver, HUH7 - in-vivo, Liver, HUH7
TrxR↓, TrxR1
ROS↑,
DNA-PK↑,
ER Stress↑,
Apoptosis↑,
eff↓, Pre-treatment with the antioxidant NAC significantly inhibited ROS generation, ER stress, DNA damage, and apoptosis induced by Sora/WA co-treatment


Showing Research Papers: 1 to 50 of 321
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 321

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

DJ-1↓, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 2,   GPx↓, 1,   GPx4↓, 1,   GSH↓, 6,   GSH∅, 1,   H2O2↑, 1,   HK1↓, 1,   HO-1↑, 1,   HO-2↑, 1,   ICD↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NRF2↝, 1,   OXPHOS↓, 2,   ROS↑, 36,   mt-ROS↑, 2,   TrxR↓, 7,   xCT↑, 1,  

Metal & Cofactor Biology ⓘ

NCOA4↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   AIF↑, 3,   ATP↓, 6,   CDC25↓, 1,   mitResp↓, 1,   MMP↓, 11,   mtDam↑, 1,   OCR↓, 1,   mt-OCR↓, 1,   Raf↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ALDOA↓, 1,   AMPK↑, 1,   p‑AMPK↑, 1,   cMyc↓, 1,   ECAR↓, 1,   ENO1↓, 1,   GlucoseCon↓, 1,   GlucoseCon∅, 1,   Glycolysis↓, 5,   HK2↓, 5,   lactateProd↓, 2,   lactateProd∅, 1,   LDHA↓, 1,   NAD↓, 1,   NADPH↓, 2,   PFK↓, 1,   PGK1↓, 1,   PI3K/Akt↓, 1,   PPP↓, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 21,   BAD↑, 1,   Bak↑, 1,   BAX↑, 8,   Bax:Bcl2↑, 2,   Bcl-2↓, 9,   Bcl-xL↓, 1,   BIM↑, 1,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 8,   cl‑Casp3↑, 2,   Casp7↑, 1,   Casp8↑, 4,   Casp9↑, 6,   cl‑Casp9↑, 2,   Cyt‑c↑, 5,   DR5↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 2,   JNK↓, 1,   MAPK↑, 1,   MDM2↓, 2,   MLKL↑, 2,   p‑MLKL↓, 1,   MOMP↑, 2,   Necroptosis↑, 3,   necrosis↑, 1,   p27↑, 1,   Paraptosis↑, 1,   survivin↓, 3,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 2,   p70S6↓, 1,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,   other↝, 4,   other∅, 1,   tumCV↓, 9,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   p‑eIF2α↑, 2,   ER Stress↓, 1,   ER Stress↑, 6,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↑, 1,   UPR↑, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

p‑Beclin-1↑, 1,   LC3B↑, 1,   LC3B-II↑, 1,   LC3s↑, 1,   p62↑, 3,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

DNA-PK↑, 2,   DNAdam↑, 12,   P53↑, 1,   p‑P53↑, 1,   p‑PARP↑, 1,   cl‑PARP↑, 7,   PCNA↓, 2,   γH2AX↑, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   E2Fs↓, 1,   P21↑, 2,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CD24↓, 1,   CD44↓, 1,   CSCs↓, 2,   ERK↓, 1,   p‑ERK↑, 1,   FOXO3↑, 1,   mTOR↓, 3,   p85S6K↓, 1,   PI3K↓, 1,   TOP2↓, 1,   TRF2↓, 1,   TumCG↓, 5,   TumCG↑, 2,  

Migration ⓘ

AP-1↓, 1,   Ca+2↝, 1,   Cdc42↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   PKCδ↓, 1,   RIP3↑, 1,   p‑RIP3↑, 2,   TIMP2↑, 1,   TumCP↓, 5,   TumMeta↓, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   Hif1a↓, 1,   Hif1a↑, 1,   VEGF↓, 2,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD4+↑, 1,   COX2↓, 1,   IKKα↓, 1,   IL8↓, 1,   NF-kB↓, 4,   p65↓, 1,   PD-L1↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 6,   Dose↓, 1,   Dose↑, 2,   Dose↝, 3,   Dose∅, 1,   eff↓, 53,   eff↑, 18,   eff↝, 1,   Half-Life↓, 2,   RadioS↓, 1,   RadioS↑, 3,   selectivity↓, 1,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

PD-L1↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   chemoP↑, 2,   OS↑, 2,   Risk↓, 1,   toxicity↓, 1,   TumVol↓, 3,   TumW↓, 4,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 192

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   GPx↑, 1,   GSH↓, 1,   GSH↑, 2,   HDL↑, 1,   MDA↓, 1,   MDA↑, 1,   NRF2↑, 1,   ROS↑, 2,   ROS∅, 2,   SOD↑, 1,   VitC↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

adiP↓, 1,   AMPK↑, 1,   glucose↑, 1,   LDL↓, 1,  

Cell Death ⓘ

Akt↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   MAPK↑, 1,   p38↑, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   p62↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   PI3K↑, 1,   PTEN↓, 1,  

Migration ⓘ

MMP9↓, 1,   PKCδ↑, 1,   TumCP↓, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature ⓘ

eNOS↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↑, 1,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

CRP↓, 1,   IL1β↓, 1,   Inflam↓, 2,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 3,   Dose∅, 1,   eff↓, 6,   eff↑, 4,   eff↝, 1,   Half-Life↑, 1,   Half-Life∅, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   GutMicro↑, 1,  

Functional Outcomes ⓘ

BOLD↑, 1,   cardioP↑, 2,   cognitive↑, 2,   memory↑, 1,   neuroP↑, 1,   Risk↓, 3,   toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 63

Scientific Paper Hit Count for: eff, efficacy
23 Sulforaphane (mainly Broccoli)
18 Magnetic Fields
16 Shikonin
12 Silver-NanoParticles
11 Copper and Cu NanoParticles
11 Baicalein
11 Piperlongumine
11 Thymoquinone
10 Ashwagandha(Withaferin A)
10 Curcumin
10 Phenethyl isothiocyanate
9 Selenite (Sodium)
8 Gambogic Acid
8 Plumbagin
6 Betulinic acid
6 Propolis -bee glue
6 Magnetic Field Rotating
5 Auranofin
5 Vitamin C (Ascorbic Acid)
5 Apigenin (mainly Parsley)
5 Artemisinin
5 Berberine
5 Parthenolide
5 Vitamin K2
4 Allicin (mainly Garlic)
4 Cisplatin
4 Disulfiram
4 EGCG (Epigallocatechin Gallate)
4 Juglone
4 doxorubicin
4 Quercetin
3 3-bromopyruvate
3 Gold NanoParticles
3 Radiotherapy/Radiation
3 Chemotherapy
3 Photodynamic Therapy
3 Alpha-Lipoic-Acid
3 Selenium
3 Capsaicin
3 Cannabidiol
3 Citric Acid
3 diet Methionine-Restricted Diet
3 Fisetin
3 Honokiol
3 Hyperthermia
3 salinomycin
3 Sulfasalazine
3 Urolithin
2 almonertinib
2 Anti-oxidants
2 Metformin
2 immunotherapy
2 borneol
2 Boron
2 Butyrate
2 Coenzyme Q10
2 Resveratrol
2 Melatonin
2 Silymarin (Milk Thistle) silibinin
2 Dichloroacetate
2 Folic Acid, Vit B9
2 erastin
2 γ-linolenic acid (Borage Oil)
2 Luteolin
2 Lycopene
2 Nimbolide
2 Phenylbutyrate
2 SonoDynamic Therapy UltraSound
2 VitK3,menadione
2 Spermidine
1 2-DeoxyGlucose
1 cetuximab
1 Anthocyanins
1 Resiquimod
1 Bevacizumab (brand Avastin)
1 Amodiaquine
1 Andrographis
1 Vitamin A, Retinoic Acid
1 Sorafenib (brand name Nexavar)
1 beta-glucans
1 5-fluorouracil
1 Bufalin/Huachansu
1 Bifidobacterium
1 Caffeic acid
1 Caffeine
1 urea
1 chitosan
1 chemodynamic therapy
1 diet FMD Fasting Mimicking Diet
1 diet Short Term Fasting
1 Ellagic acid
1 Emodin
1 Electrical Pulses
1 Exercise
1 Fenbendazole
1 Garcinol
1 Hydrogen Gas
1 HydroxyCitric Acid
1 tamoxifen
1 hydroxychloroquine
1 HydroxyTyrosol
1 lambertianic acid
1 Methylene blue
1 Matrine
1 Methyl Jasmonate
1 Methylsulfonylmethane
1 Myricetin
1 Propyl gallate
1 Piperine
1 Rosmarinic acid
1 Oxaliplatin
1 Scoulerine
1 Aflavin-3,3′-digallate
1 Ursolic acid
1 Vitamin B5,Pantothenic Acid
1 Wogonin
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#:%  Target#:961  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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