GSH Cancer Research Results

GSH, Glutathione: Click to Expand ⟱

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Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.

Scientific Papers found: Click to Expand⟱

2327-

2DG,

2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents

Review,

Var,

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

1339-

2DG,

Cisplatin,

2-Deoxy-d-Glucose Combined with Cisplatin Enhances Cytotoxicity via Metabolic Oxidative Stress in Human Head and Neck Cancer Cells

in-vitro,

HNSCC,

FaDu

ChemoSen↑, combination of 2DG and cisplatin resulted in a significant decrease in cell survival when compared with 2DG or cisplatin alone
ROS↑,
GSH↓,
other↓, Simultaneous treatment with the thiol antioxidant N-acetylcysteine (NAC) inhibited parameters indicative of oxidative stress, as well as protected FaDu cells from the cytotoxic effects of cisplatin alone and the combination of 2DG and cisplatin.

1341-

3BP,

The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate

Review,

NA,

Glycolysis↓, second-generation glycolysis inhibitor.
OXPHOS↓,
*toxicity↓, Normal cells remain unharmed
ROS↑, well known that this compound generates ROS
GSH↓,
eff↑, 3BP demonstrates synergistic activity with other compounds that reduce intracellular levels of GSH

5271-

3BP,

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

Review,

Var,

selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

5282-

3BP,

Rad,

3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MDA-MB-468

Glycolysis↓, Metabolomic analyses showed that 3BP causes inhibition of glycolysis
RadioS↑, Overall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs
eff↑, 3BP is selectively toxic to cells expressing MCT1
GAPDH↓, 3BP inhibits GAPDH but not hexokinase
PPP↑, Pentose phosphate pathway is upregulated in response to 3BP
GSH↓, Glutathione and NADH are depleted at early time points
ECAR↓, prolonged incubation with 20 μM 3BP for 24 h resulted in a statistically significant selective decrease in ECAR

5277-

3BP,

3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model

in-vivo,

PC,

Panc02

mouse model

HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5273-

3BP,

The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view

Review,

Var,

AntiCan↑, 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect.
ROS↑,
angioG↓,
CSCs↓,
Warburg↓,
GSH↓, Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i
Thiols↓, Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH.

5263-

3BP,

CET,

3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis

in-vitro,

CRC,

DLD1

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↑,

5257-

3BP,

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Review,

Var,

Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

5459-

AF,

Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

in-vitro,

Ovarian,

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);

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.

5434-

AG,

Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

Review,

Liver,

AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

1902-

AgNPs,

Modulation of the mechanism of action of antibacterial silver N-heterocyclic carbene complexes by variation of the halide ligand

in-vitro,

NA,

0.03–0.12 μM

bacterial

TrxR↓, antibacterial silver NHC complexes with halide ligands of the general type (NHC)AgX (X = Cl, Br or I) that showed potent inhibition of purified bacterial thioredoxin reductase (TrxR) and glutathione reductase (GR
GSR↓,
GSH↓, glutathione (GSH) depletion

4417-

AgNPs,

Caffeine-boosted silver nanoparticles target breast cancer cells by triggering oxidative stress, inflammation, and apoptotic pathways

in-vitro,

BC,

MDA-MB-231

ROS↑, Caf-AgNPs significantly increased ROS, malondialdehyde, COX-2, IL-1β, and TNF-α level in BC cells, which was accompanied by a decrease in glutathione levels.
MDA↑,
COX2↑,
IL1β↑,
TNF-α↑,
GSH↓,
Cyt‑c↑, increased levels of cytosolic cytochrome c, caspase-3, and Bax proteins, as well as a significant decrease in Bcl-2 expression and Bcl-2/Bax ratio
Casp3↑,
BAX↑,
Bcl-2↓,
LDH↓, Cancer cells subjected to Caf-AgNPs demonstrated elevated lactate dehydrogenase (LDH) membrane leakage
cycD1/CCND1↓, notable downregulation of cyclin D1 and cyclin-dependent kinase 2 (CDK2) mRNA expression
CDK2↓,
TumCCA↑, several mechanisms for cellular destruction, including cell cycle arrest, oxidative stress induction, modulation of the inflammatory response, and mitochondrial apoptosis
mt-Apoptosis↑,

4382-

AgNPs,

Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism

in-vitro,

Nor,

RAW264.7

68.9 nm, concentrations; 0.2, 0.4, 0.8, and 1.6 ppm, exposure time; 24, 48, 72, and 96 h

*GSH↓, AgNPs decreased intracellular glutathione level, increased NO secretion, increased TNF-α in protein and gene level
*NO↑,
*TNF-α↑,
*MMP3↑, increased gene expression of matrix metalloproteinases (MMP-3, MMP-11, and MMP-19).
*MMP11↑,

4439-

AgNPs,

Anticancer Potential of Green Synthesized Silver Nanoparticles Using Extract of Nepeta deflersiana against Human Cervical Cancer Cells (HeLA)

in-vitro,

Cerv,

HeLa

33 nm

ROS↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
lipid-P↑,
MMP↓,
GSH↓,
TumCCA↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
Apoptosis↑,
Necroptosis↑,
TumCD↑, AgNPs-induced cell death in HeLA cells suggested the anticancer potential of ND-AgNPs.
Dose↝, ND-AgNPs at 10, 25, and 50 µg/ml concentration

4371-

AgNPs,

Effects of Green Silver Nanoparticles on Apoptosis and Oxidative Stress in Normal and Cancerous Human Hepatic Cells in vitro

in-vitro,

Liver,

HUH7

20−50 nm

eco-friendly approach silver nanoparticles (AgNPs) using root extracts of Beta vulgaris L.

ROS↑, The gAgNPs induced more ROS in the HuH-7 cells than in the CHANG cells.
selectivity↑, HuH-7 cells showed an increased sensitivity to gAgNPs than the CHANG cells.
DNAdam↑, higher concentrations of gAgNPs may induce significant cytotoxicity and cause DNA damage and apoptosis.
Apoptosis↑,
GSH↓, The level of glutathione was decreased (Figure 4B) and lipid peroxide was increased in HuH-7 cells than CHANG cells (Figure 4A).
lipid-P↑,
MMP↓, indicating loss of MMP
DNAdam↑, higher DNA damage was seen in HuH-7 cells than CHANG cells

5143-

AgNPs,

Thermal Co-reduction engineered silver nanoparticles induce oxidative cell damage in human colon cancer cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

in-vitro,

CRC,

HCT116

28.11 μg/ml.

ROS↑, AgNP induces oxidative stress on HCT116 by increased levels of lipid peroxidation and reduced levels of glutathione.
lipid-P↑,
GSH↓,
MMP↓, Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis.
Casp3↑,
Apoptosis↑,
TumCCA↑, Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis.

335-

AgNPs,

PDT,

Biogenic Silver Nanoparticles for Targeted Cancer Therapy and Enhancing Photodynamic Therapy

Review,

NA,

ROS↑,
GSH↓,
GPx↑,
Catalase↓,
SOD↓,
p38↑,
BAX↑,
Bcl-2↓,

324-

AgNPs,

CPT,

Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells

in-vitro,

Cerv,

HeLa

ROS↑,
Casp3↑,
Casp9↑,
Casp6↑,
GSH↓,
SOD↓,
GPx↓,
MMP↓, loss of
P53↑,
P21↑,
Cyt‑c↑,
BID↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
Akt↓,
Raf↓,
ERK↓,
MAP2K1/MEK1↓,
JNK↑,
p38↑,

344-

AgNPs,

Cytotoxicity and ROS production of manufactured silver nanoparticles of different sizes in hepatoma and leukemia cells

in-vitro,

Liver,

HepG2

ROS↑,
GSH↓,

373-

AgNPs,

Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116

in-vitro,

Colon,

HCT116

LDH↓, Increased lactate dehydrogenase leakage (LDH),
ROS↑,
MDA↑,
ATP↓,
GSH↓,
MMP↓, loss of

372-

AgNPs,

Investigating oxidative stress and inflammatory responses elicited by silver nanoparticles using high-throughput reporter genes in HepG2 cells: effect of size, surface coating, and intracellular uptake

in-vitro,

Hepat,

HepG2

NRF2↑,
GSH↓,

369-

AgNPs,

Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

in-vitro,

Liver,

ROS↑,
GSH↓,
DNAdam↑,
lipid-P↝, damage
Apoptosis↑,
BAX↑,
Bcl-2↓,
MMP↓, disruption
Casp9↑,
Casp3↑,
JNK↑,

398-

AgNPs,

Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-β/α-SMA upregulation in rats

in-vivo,

Testi,

rats

Bcl-2↓,
Casp3↑,
GSH↓,
MDA↑,
NO↑,
H2O2↑,
SOD↓,

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↑,

2836-

AgNPs,

Gluc,

Glucose capped silver nanoparticles induce cell cycle arrest in HeLa cells

in-vitro,

Cerv,

HeLa

eff↝, AgNPs synthesized are stable up to 10 days without silver and glucose dissolution.
TumCCA↑, AgNPs block the cells in S and G2/M phases, and increase the subG1 cell population.
eff↑, HeLa cells take up abundantly and rapidly AgNPs-G resulting toxic to cells in amount and incubation time dependent manner.
eff↑, The dissolution experiments demonstrated that the observed effects were due only to AgNPs-G since glucose capping prevents Ag+ release.
ROS↑, AgNPs cause toxic responses via induction of oxidative stress as consequence of the generation of intracellular (ROS), depletion of glutathione (GSH), reduction of the superoxide dismutase (SOD) enzyme activity, and increased lipid peroxidation
GSH↓,
SOD↓,
lipid-P↑,
LDH↑, significant LDH levels increase with the highest amount of AgNPs-G and maximum of toxicity was seen at 12 h.

2660-

AL,

Allicin: A review of its important pharmacological activities

Review,

AD,

Review,

Var,

Review,

Park,

Review,

Stroke,

*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

2667-

AL,

Allicin in Digestive System Cancer: From Biological Effects to Clinical Treatment

Review,

GC,

AntiCan↑, Allicin not only protects against tumors but also alleviates the adverse effects of anticancer treatment and enhances the chemotherapeutic response under certain conditions.
ChemoSen↑,
angioG↓, DATS works against tumors by blocking the cell cycle, inhibiting tumor cell proliferation, and inhibiting angiogenesis
chemoP↑,
*GutMicro↑, In addition to against bacteria, allicin has also been shown to modulate the composition of gut microbiota (GM) and increase the diversity of beneficial bacteria in animal models
*antiOx↑, allicin was confirmed to have strong antioxidant properties
other↝, Allicin is a reactive sulfur species (RSS) and a potent thiol-trapping reagent, rapidly reacting with glutathione (GSH) to yield S-allylmercaptoglutathione (GSSA)
GSH↓, Thus, allicin depletes the intracellular GSH pool and reacts with cysteine thiols available in proteins through S-thioallylation
Thiols↓, This reaction is the key to the biological activity of allicin, and the reversible oxidation and reduction of protein-thiols is the core of many processes in cells
*ROS↓, In a hypertrophic heart mouse model, the clearance of intracellular ROS by allicin was measured, and has been shown to reduce the production of ROS and block ROS-dependent ERK1/2, JNK1/2, AKT, NF-κB and Smad signaling, which leads to the inhibition o
*hepatoP↑, Moreover, allicin has been proven to play a hepatoprotective role against acetaminophen (APAP)-induced liver injury by reducing oxidative stress
*Inflam↓, OSCs in garlic has been shown to inhibit the tumor-mediated pro-inflammatory activity by modulating the cytokine pattern in a way that leads to an overall inhibition of NF-κB
*NF-kB↓,

254-

AL,

Allicin and Cancer Hallmarks

Review,

Var,

NRF2⇅, 40 nM
BAX↑,
Bcl-2↓,
Fas↑,
MMP↓,
Bax:Bcl2↑,
Cyt‑c↑,
Casp3↑,
Casp12↑,
GSH↓, Allicin can easily penetrate the cell membrane and react with the cellular thiol to transiently deplete the intracellular GSH level, inducing the inhibition of cell cycle progression and growth arrest [98].
TumCCA↑,
ROS↑, An in vitro study indicated that allicin encourages oxidative stress and autophagy in Saos-2 and U2OS (osteosarcoma cells) by modulating the MALATI-miR-376a-Wnt and β-catenin pathway [99].
antiOx↓, As an antioxidant phytochemical, it scavenges reactive oxygen species (ROS) and protects cells from oxidative DNA damage [34].

236-

AL,

Allicin: Chemistry and Biological Properties

Analysis,

NA,

GSH↓, allicin reacts with GSH
Bacteria↓, Antimicrobial
LDL↓, reduction without altering HDL
ROS↑, antioxidant at low doses
NRF2↑,
cognitive↑, by activating the Nrf2-system
memory↑, by activating the Nrf2-system
BP↓, via H2S generation
RNS↓,

5167-

AL,

The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines

in-vitro,

Nor,

3T3

in-vitro,

BC,

MCF-7

in-vitro,

Lung,

A549

in-vitro,

CRC,

HT-29

Thiols↓, Garlic produces the thiol-reactive defence substance, allicin, upon wounding.
tumCV↓, Allicin reduced cell viability and cell proliferation in a concentration dependent manner.
TumCP↓, Allicin Inhibits Cell Proliferation
GSH↓, allicin reacts with and depletes the GSH pool.
GSSG↑, Allicin is a thiol-reagent and reacts easily with glutathione, forming S-allylmercaptoglutathione (GSSA) and leading to an increased production of GSSG
ROS↑, Allicin oxidizes thiols and causes oxidative stress in its own right.

5165-

AL,

The human allicin-proteome: S-thioallylation of proteins by the garlic defence substance allicin and its biological effects

in-vitro,

AML,

Jurkat

in-vitro,

Nor,

L929

necrosis↑, Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades.
Thiols↓, Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects.
GSH↓,
ENO1↓, allicin caused inhibition of enolase activity, an enzyme considered a cancer therapy target.
Zn2+↑, Allicin leads to Zn2+ release in murine EL-4 cells
Glycolysis↓, suggests that allicin can inhibit glycolysis which provides electron donors for ATP generation required for cellular biosynthesis pathways and growth of the cells.
ATP↓,
BioAv↓, achieving therapeutically relevant concentrations of allicin via the oral route is therefore unlikely and more direct routes of application to the desired site of action need to be considered

1349-

And,

Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction

in-vitro,

Lung,

H460

33.16 μM

in-vitro,

Lung,

H1650

32.45 μM

TumCG↓,
TumMeta↓,
Ferroptosis↑,
ROS↑,
MDA↑,
Iron↑,
GSH↓, lipid ROS reduced glutathione (GSH) accumulation
GPx4↓,
xCT↓, SLC7A11
MMP↓,
ATP↓,

1547-

Api,

Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading

Review,

NA,

angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

1565-

Api,

Apigenin-7-glucoside induces apoptosis and ROS accumulation in lung cancer cells, and inhibits PI3K/Akt/mTOR pathway

in-vitro,

Lung,

A549

 25,  50, 100, and 200 μM AGL

in-vitro,

Nor,

BEAS-2B

in-vitro,

Lung,

H1975

TumCP↓, AGL significantly reduced proliferation, promoted cell apoptosis, and attenuated the migration and invasion of A549 or H1975 cell
Apoptosis↑,
TumCMig↓,
TumCI↓,
Cyt‑c↑, elevated the levels of cytochrome C and MDA
MDA↑,
GSH↓, but reduced the production of GSH in A549 and H1975 cells.
ROS↑, AGL enhanced the accumulation of ROS
PI3K↓, induces ROS accumulation in lung cancer cells by repressing PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,

1564-

Api,

Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation

in-vitro,

Pca,

22Rv1

10–80 μM

in-vivo,

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%

3382-

ART/DHA,

Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?

Review,

Var,

1.20–15.2 μM

AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
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
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
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.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
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

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

29.4±1.7 µM

in-vitro,

Liver,

HUH7

32.1±4.5 µM

in-vitro,

Liver,

HepG2

40.2±2.1 µM

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

3387-

ART/DHA,

Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment

Review,

Var,

BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
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.
Ferroptosis↑,
Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
GPx4↓, GPX4-dependent defense system is significantly inhibited
GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
PERK↑,
ATF4↑,
GRP78/BiP↑,
CHOP↑, which activates CHOP
ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
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

3389-

ART/DHA,

Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers

Review,

Var,

GSH↓, decreasing cellular GSH levels and the presence of iron-induced ROS generation
ROS↑,
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
eff↑, Therefore, the combination of ART with NRF2 genetic silencing or trigonelline may provide a preferable efficacy

3345-

ART/DHA,

Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells

in-vitro,

GBM,

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
Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
lipid-P↑,
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)
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)
ATF4↑,
GRP78/BiP↑, HSPA5
MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
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

3395-

ART/DHA,

Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis

in-vitro,

NA,

HSC-T6

 Liver Fibrosis LX2

*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
*GSH↓,
*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

5378-

ART/DHA,

Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives

Review,

Var,

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]

2570-

ART/DHA,

Discovery, mechanisms of action and combination therapy of artemisinin

Review,

Nor,

*BioAv↓, Because the parent drug of artemisinin is poorly soluble in water or oil, the carbonyl group of artemisinin was reduced to obtain DHA
*Half-Life↓, artemisinins also have a very short elimination half-life (∼1 h)
*toxicity↓, Artemisinin and its derivatives are generally safe and well-tolerated.
*ROS↑, Artemisinins are considered prodrugs that are activated to generate carbon-centered free radicals or reactive oxygen species (ROS).
GSH↓, earlier studies suggest that artemisinins modulate parasite oxidative stress and reduce the levels of antioxidants and glutathione (GSH) in the parasite
selectivity↑, Many publications corroborate the essence of iron-dependent bioactivation

3176-

Ash,

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex

in-vitro,

NA,

Leishmanial cell- parasites

PKCδ↓, inhibition of PKC by withaferin A is a central event for the induction of apoptosis
TOP1∅, This result suggests that withaferin A and staurosporine do not inhibit topoisomerase I in vitro.
ROS↑, Withaferin A induces oxidative stress, causes decrease in GSH level and leads to subsequent DNA lesions
GSH↓,
DNAdam↑,
MMP↓, Withaferin A inhibits growth of L. donovani promastigotes, induces depolarization of mitochondrial membrane potential and releases cytochrome c into the cytosol.
Cyt‑c↑,

3172-

Ash,

Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis

in-vitro,

HCC,

HepG2

in-vitro,

Nor,

HL7702

Keap1↑, Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression
NRF2↓,
EMT↓, Withaferin A suppresses epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer
TumCP↓, Withaferin A restrains proliferation, invasion, and VM of hepatoma cells while preserving normal hepatocytes
TumCI↓,
selectivity↑, , treatment with Withaferin A ranging from 1 to 100 μM had little effect on cell viability of human normal liver cells (HL-7702 cells), indicating the little cytotoxicity on normal hepatocytes.
*toxicity↓,
ROS↑, Withaferin A strikingly enhanced ROS () and MDA levels (), but reduced the GSH levels (), indicating the induction of ferroptosis by Withaferin A
MDA↑,
GSH↓,
Ferroptosis↑,

3163-

Ash,

Rad,

Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis

*radioP↑, Withaferin A (WA) protected only normal lymphocytes, but not cancer cells, against IR-induced apoptosis
selectivity↑,
*Casp3↓, WA treatment led to significant inhibition of IR-induced caspase-3 activation and decreased IR-induced DNA damage to lymphocytes and bone-marrow cells.
*DNAdam↓,
*ROS↓, WA reduced intracellular ROS and GSH levels
*GSH↓,
*NRF2↑, WA induced pro-survival transcription factor, Nrf-2, and expression of cytoprotective genes HO-1, catalase, SOD, peroxiredoxin-2 via ERK.
*HO-1↑,
*Catalase↑,
*SOD↑,
*Prx↑,
*ERK↑, Activated ERK promotes the nuclear translocation and activity of Nrf2

1146-

AsP,

Potential use of nanoformulated ascorbyl palmitate as a promising anticancer agent: First comparative assessment between nano and free forms

in-vivo,

Nor,

Ehrlich ascites carcinoma (EAC)-bearing mice

TumCCA↑, G2/M phase
Apoptosis↑,
IL6↓,
STAT3↓,
angioG↓,
TumMeta↓,
VEGF↓,
MMP9↓,
SOD↑,
Catalase↑,
GSH↓,
MDA↓,
NO↓,
*BioAv↑, nano particles

5362-

AV,

Anti-cancer effects of aloe-emodin: a systematic review

Review,

Var,

AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

Showing Research Papers: 1 to 50 of 223
Page 1 of 5 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 223

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 213

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 1, Ferroptosis↑, 1, GSH↓, 4, GSH↑, 1, GSTs↑, 1, HO-1↑, 1, Keap1↓, 1, lipid-P↓, 1, MDA↓, 1, MDA↑, 1, MPO↓, 1, NRF2↑, 2, Prx↑, 1, ROS↓, 4, ROS↑, 2, SOD↑, 2, TBARS↓, 1,

Mitochondria & Bioenergetics ⓘ

ATP↓, 1, MMP↓, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, H2S↑, 1, LDH↓, 2,

Cell Death ⓘ

Akt↓, 1, BAX↑, 1, Bcl-2↓, 1, Casp3↓, 1, Casp3↑, 1, Ferroptosis↑, 1, iNOS↓, 1,

Transcription & Epigenetics ⓘ

other↑, 1,

Autophagy & Lysosomes ⓘ

LC3II↑, 1, p62↑, 1,

DNA Damage & Repair ⓘ

DNAdam↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1, PI3K↓, 1,

Migration ⓘ

MMP11↑, 1, MMP3↑, 1, ROCK1↓, 1, TumCP↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1, NO↑, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL6↓, 1, Inflam↓, 2, NF-kB↓, 2, PGE2↓, 1, TNF-α↓, 1, TNF-α↑, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1, eff↓, 1, eff↑, 1, Half-Life↓, 1, Half-Life↝, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, AST↓, 1, BP↓, 1, creat↓, 1, GutMicro↑, 2, IL6↓, 1, LDH↓, 2,

Functional Outcomes ⓘ

cardioP↑, 1, cognitive↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 2, radioP↑, 1, toxicity↓, 3,
Total Targets: 70

Scientific Paper Hit Count for: GSH, Glutathione

18 Piperlongumine
16 Silver-NanoParticles
12 Phenethyl isothiocyanate
11 Sulfasalazine
11 Shikonin
10 Curcumin
9 Quercetin
8 Artemisinin
8 Selenite (Sodium)
7 3-bromopyruvate
7 Radiotherapy/Radiation
7 diet Methionine-Restricted Diet
6 Allicin (mainly Garlic)
6 Juglone
6 Propyl gallate
6 Sulforaphane (mainly Broccoli)
6 Thymoquinone
5 Boron
5 erastin
4 Apigenin (mainly Parsley)
4 Copper and Cu NanoParticles
4 Luteolin
4 Vitamin C (Ascorbic Acid)
3 Cisplatin
3 Auranofin
3 Ashwagandha(Withaferin A)
3 Baicalein
3 Chrysin
3 Parthenolide
3 Silymarin (Milk Thistle) silibinin
3 Aflavin-3,3′-digallate
2 2-DeoxyGlucose
2 Bromelain
2 brusatol
2 Selenium
1 cetuximab
1 Astragalus
1 Photodynamic Therapy
1 Camptothecin
1 Glucose
1 Andrographis
1 Ascorbyl Palmitate
1 Aloe anthraquinones
1 Berberine
1 Betulinic acid
1 Ras-selective lethal 3
1 Capsaicin
1 chitosan
1 Citric Acid
1 Black phosphorus
1 SonoDynamic Therapy UltraSound
1 Ellagic acid
1 Emodin
1 Ferulic acid
1 Garcinol
1 Hyperthermia
1 HydroxyTyrosol
1 Chemotherapy
1 Lycopene
1 Melatonin
1 Metformin
1 Magnetic Field Rotating
1 Magnetic Fields
1 Myricetin
1 Naringin
1 Propolis -bee glue
1 Plumbagin
1 Resveratrol
1 Rosmarinic acid
1 salinomycin
1 Scoulerine
1 Selenium NanoParticles
1 Docetaxel
1 Glutathione
1 Gemcitabine (Gemzar)
1 immunotherapy
1 VitK3,menadione

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#:137  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

GSH Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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