H2O2 Cancer Research Results

H2O2, Hydrogen peroxide (H2O2): Click to Expand ⟱

Source:

Type:

H2O2 is a reactive oxygen species (ROS) that can induce oxidative stress in cells. While low levels of ROS can promote cell signaling and proliferation, high levels can lead to DNA damage, apoptosis (programmed cell death), and other cellular dysfunctions. This dual role means that H2O2 can contribute to cancer development and progression, as oxidative stress can lead to mutations and genomic instability.
H2O2 can enhance the effectiveness of certain chemotherapeutic agents by increasing oxidative stress in cancer cells. Additionally, localized delivery of H2O2 has been explored as a means to selectively target and kill cancer cells while sparing normal cells.
Cancer cells often exhibit altered metabolism, leading to increased production of reactive oxygen species, including H2O2. This can result from enhanced mitochondrial activity, increased glycolysis, or other metabolic adaptations that are characteristic of cancer.

Reported H2O2 concentrations for representative compounds.

Prooxidant	Dose	Cell Line	H2O2 Produced
EGCG	50 µM	Jurkat	~1 µM
EGCG	10 µM	HCT116 and HT29	1.5 µM
EGCG	100 µM	Jurkat	20 µM
Quercetin	70 µM	HT29	2 µM
Menadione	10 µM	Jurkat	20 µM
Plumbagin	4 µM	SiHA and HeLa	1 mM
β-Lap	1 µM	HL-60	70 µM
Doxorubicin	1 µM	PC3	38 pM
Ascorbic Acid	1 mM	HL-60	161 µM
Ascorbic Acid	0.2–2.0 mM	Lymphoma	20–120 µM
Ascorbic Acid	i.v. 0.5 mg/g	Rats	0–20 µM
Ascorbic Acid	i.p. 4.0 g/kg	Mice tumor	> 125 µM
TiO2	10 µg/mL	HepG2	150 nmol/mL
Paclitaxel	100 nM	MCF7	600 nM
Paclitaxel	100 nM	HL-60	1100 nM

Note: many products at lower concentrations act as antioxidants, instead of Prooxidants.

Generally, increased hydrogen peroxide and oxidative stress are associated with poor outcomes, while the specific context and cellular environment can modulate its effects.

Scientific Papers found: Click to Expand⟱

1340-

3BP,

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study

Review,

NA,

Glycolysis↓, inhibiting key glycolysis enzymes
HK2↓,
LDH↓,
OXPHOS↓, inhibits mitochondrial oxidative phosphorylation
angioG↓,
H2O2↑, induces hydrogen peroxide generation in cancer cells (oxidative stress effect)
eff↑, Concurrent use of a GSH depletor(paracetamol) with 3BP killed resistant melanoma cells

353-

AgNPs,

The mechanism of cell death induced by silver nanoparticles is distinct from silver cations

in-vitro,

BC,

SUM159

 TNBC

lipid-P↑, caused by AgNPs not Ag+
H2O2↑, caused by Ag+
ROS↑,
Apoptosis↑,

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↓,

5340-

Ajoene,

Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB

in-vitro,

AML,

Apoptosis↑, The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors.
selectivity↑,
H2O2↑, Ajoene increased the production of intracellular peroxide in a dose- and time-dependent fashion, which could be partially blocked by preincubation of the human leukemic cells with the antioxidant N-acetylcysteine.
NF-kB↑, These results suggested that ajoene might induce apoptosis in human leukemic cells via stimulation of peroxide production and activation of nuclear factor kappaB.

252-

Ajoene,

Ajoene, a Compound of Garlic, Induces Apoptosis in Human Promyeloleukemic Cells, Accompanied by Generation of Reactive Oxygen Species and Activation of Nuclear Factor κB

in-vitro,

AML,

HL-60

 10uM

H2O2↑,
NF-kB↑, Activation of Nuclear Factor κB
ROS↑,

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

0-100uM

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

1526-

Ba,

Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells

in-vitro,

AML,

HL-60

25uM

Apoptosis↑, 100 microM for 6 h
cl‑PARP↑,
DNAdam↑, DNA fragmentation.
cl‑BID↑,
Cyt‑c↑, cytochrome c release from mitochondria into cytosol
Casp3↑,
Casp8↑,
Casp9?,
H2O2↑, baicalein caused elevation of intracellular hydrogen peroxide level
ROS↑, apoptotic death program through reactive oxygen species (ROS)-mediated mitochondrial dysfunction pathway

2606-

Ba,

Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma

Review,

HCC,

ChemoSen↑, In addition, the combination of baicalein and silymarin eradicates HepG2 cells efficiently superior to baicalein or silymarin alone
TumCP↓, Cell viability assays have demonstrated that baicalein is significantly cytotoxic against several HCC cell lines and can inhibit the proliferation of HCC cells through arresting the cell cycle.
TumCCA↑,
TumCMig↓, Baicalein has been proved to inhibit migration and invasion of human HCC cells by reducing the expression and their proteinase activity of matrix metalloproteinases (MMPs),
TumCI↓,
MMPs↓,
MAPK↓, A large number of studies found that baicalein could inhibit migration and invasion of cancer cells by targeting the MAPK, TGF-b/Smad4, GPR30 pathway and molecules such as, ezrin, zinc-finger protein X-linked (ZFX),
TGF-β↓,
ZFX↓,
p‑MEK↓, Baicalein could inhibited the phosphorylation of MEK1 and ERK1/2, leading to decreased expression and proteinase activity of MMP-2/9 and urokinase-type plasminogen activator (u-PA),
ERK↓,
MMP2↓,
MMP9↓,
uPA↓,
TIMP1↓, as well as increased expression of TIMP-1 and TIMP-2
TIMP2↓,
NF-kB↓, Additionally, the nuclear translocation of NF-kB/p50 and p65/RelA and the phosphorylation of I-kappa-B (IKB)-b could be down-regulated by baicalein
p65↓,
p‑IKKα↓,
Fas↑, Hep3 B cells via activating Fas, Caspase -2, -3, -8, -9, down-regulating Bcl-xL, and upregulating Bax [
Casp2↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
BAX↑,
ER Stress↑, baicalein could induced apoptosis via endoplasmic reticulum (ER) stress in SMMC-7721 and Bel-7402
Ca+2↑, increasing intracellular calcium(Ca2+ ), and activating JNK pathwa
JNK↑,
P53↑, selectively induce apoptosis in HCC J5 cells via upregulation of p53
ROS↑, baicalein could induced cell apoptosis through regulating ROS via increasing intracellular H2O 2 level [
H2O2↑,
cMyc↓, baicalein could promote apoptosis in HepG2 and Bel-7402 cells through inhibiting c-Myc and CD24 expression
CD24↓,
12LOX↓, baicalein could induced cell apoptosis in SMMC-7721 and HepG2 cells by specifically inhibiting expression of 12-lipoxygenase(12-LOX), a critical anti-apoptotic genes

603-

Catechins,

Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species

in-vitro,

NA,

HL-60

ROS↑,
DNAdam↑,
H2O2↑,

2806-

CHr,

Se,

Selenium-containing chrysin and quercetin derivatives: attractive scaffolds for cancer therapy

in-vitro,

Var,

eff↑, SeChry elicited a noteworthy cytotoxic activity with mean IC50 values 18- and 3-fold lower than those observed for chrysin and cisplatin, respectively
selectivity↑, differential behavior toward malignant and nonmalignant cells was observed for SeChry and SePQue, exhibiting higher selectivity indexes
Dose↝, 5 min. of microwave irradiation at 175 W (150 ºC) of an acetonitrile WR and flavonoid solution on a sealed pyrex microwave vial,
TrxR↓, Both compounds were able to decrease cellular TrxR
GSH↓, The results clearly showed that after treatment with both seleno-flavonoids total glutathione concentration (GSH + GSSG) decreased
MMP↓, MMP reduced by up to four times compared to control cells
ROS↑, Both seleno-derivatives were able to increase the oxidant basal production
H2O2↑, ore dramatic decrease of the MMP and a higher ability to increase the hydrogen peroxide basal production,

1585-

Citrate,

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer

in-vitro,

Ovarian,

SKOV3

15.93 mM

in-vitro,

Ovarian,

A2780S

16.8 mM

in-vitro,

Nor,

HEK293

Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1602-

Cu,

A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy†

in-vitro,

BC,

MCF-7

3.2uM

in-vitro,

BC,

4T1

3.3uM

in-vitro,

Lung,

A549

4uM

in-vitro,

Liver,

HepG2

3.5uM

eff↑, enhanced chemodynamic cancer therapy
GSH↓, glutathione (GSH) depletion properties
H2O2↑, overexpressed H2O2
ROS↑, highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells
*BioAv↑, complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus
selectivity↑, toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2
TumCCA↑, arrest the cell cycle of the G0/G1 phase
Apoptosis↑, inducing apoptosis rather than necrosis
Fenton↑, Cu+-involved reaction can occur with a highest reaction rate (1x10E4 M-1 s-1) in weakly acidic, which is about 160-fold increase over that of Fe2+
*toxicity?, C50 value of CuL-Cuphen to normal cells COS-7 was about 6.3uM.

1596-

Cu,

CDT,

Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review

Review,

NA,

TumCD↑, Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and p
Apoptosis↓,
ROS↑,
angioG↑,
Cupro↑,
Paraptosis↑,
eff↑, copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy.
eff↓, Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes
selectivity↑, Copper nanoparticles also can selectively attack cancer cells and spare healthy cells This selectivity is attributed to the EPR effect, which enables nanoparticles to accumulate in tumor tissue by exploiting leaky blood vessels
DNAdam↑, Copper has been found to induce DNA damage and oxidation through the formation of ROS.
eff↑, Tumor cells suffering from oxygen deficiency often have an increased concentration of CTR-1, which facilitates the transport of copper(I) into the cells
eff↑, The results demonstrate the promising capabilities of 64CuCl2 as a valuable tool for both diagnosis and therapy in various types of cancer
eff↑, nanoparticles have remarkable properties, including a large surface area to volume ratio, excellent compatibility with living organisms, and the ability to generate ROS when exposed to an acidic tumor microenvironment
eff↑, Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy (CDT)
Fenton↑, CDT is a promising treatment strategy for cancer that utilizes the in situ Fenton reaction, which is activated by endogenous substances, such as GSH and H2O2 without the need for external energy input
H2O2↑, Copper-based substrates have been developed that generate H2O2 internally and function effectively in weakly acidic tumor microenvironments (TME)
eff↑, metal peroxide nanomaterials and offers a promising strategy to improve CDT efficacy
eff↑, Copper nanoparticles can also be used in phototherapy
eff↑, Copper nanoparticles have also shown success in destroying cancer tissue by hyperthermia. This method is a local anticancer treatment in which cells are exposed to high temperatures.
RadioS↑, promising results when used in combination with radiotherapy or chemotherapy for various tumor types.
ChemoSen↑,
eff↑, copper nanoparticles are promising in cancer immunotherapy because they enhance immune-based therapies
*toxicity↝, Copper is a necessary trace mineral for the human body, but high concentrations of copper can be toxic
other↑, Extensive research has shown that cancer cells require an increased copper content to support their rapid growth compared to normal cells
eff↑, Copper nanoparticles can be used to generate heat when exposed to certain wavelengths of light or alternating magnetic fields.

1889-

DCA,

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth

Review,

Var,

PDKs↓, Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK)
Glycolysis↓, shifts metabolism from glycolysis to glucose oxidation
mt-H2O2↑, increases mitochondrial H2O2
Apoptosis↑, DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity
TumCP↓,
TumCG↓,
toxicity∅,

1846-

dietFMD,

VitC,

A fasting-mimicking diet and vitamin C: turning anti-aging strategies against cancer

Study,

Var,

TumCG↓, FMDs delay tumor progression
ChemoSen↑, potentiate chemotherapy efficacy
ChemoSideEff↓, while protecting healthy tissues from chemo-associated side effects in different cancer models
ROS↑, presence of metals, and particularly iron, high dose of vitamin C exerts a pro-oxidant action by generating hydrogen peroxide and hydroxyl radicals via Fenton chemistry
Fenton↑,
H2O2↑,
eff↑, we show that FMD cycles potentiate high-dose vitamin C anti-cancer effects in a range of cancer types
HO-1↓, KRAS-mutant cancer cells respond to vitamin C treatment by up-regulating HO-1, and consequently limiting vitamin C pro-oxidant action. FMD is able to revert HO-1 up-regulation
DNAdam↑, increase in free reactive iron and oxygen species causing DNA damage and cell death
eff↑, we found that the nontoxic FMD + vitamin C combination therapy is as effective as oxaliplatin + vitamin C in delaying tumor progression while the triple FMD, vitamin C and chemotherapy combination treatment is the most effective.

1012-

EGCG,

Inhibition of beta-catenin/Tcf activity by white tea, green tea, and epigallocatechin-3-gallate (EGCG): minor contribution of H(2)O(2) at physiologically relevant EGCG concentrations

in-vitro,

Nor,

HEK293

10-12uM EGCG

*H2O2↑,
*β-catenin/ZEB1↓,
*TCF-4↓,

643-

EGCG,

New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate

Analysis,

NA,

H2O2↑,
Fenton↑,
PDGFR-BB↑,
EGFR↓, EGCG inhibits activities of EGFR, VEGFR, and IGFR
VEGFR2↓,
IGFR↓,
Ca+2↑, EGCG elevates cytosolic Ca2+ levels
NO↑, EGCG-stimulated elevation of cytosolic calcium contributes to NO production by binding to calmodulin
Sp1/3/4↓,
NF-kB↓,
AP-1↓,
STAT1↓,
STAT3↓,
FOXO↓, FOXO1
mtDam↑,
TumAuto↑,

642-

EGCG,

Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect

ROS↑, under high-dose conditions. Autooxidation of EGCG generates substantial ROS
H2O2↑, One EGCG molecule could produce more than two H2O2 molecules
Apoptosis↑,
Trx↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
TrxR↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
JNK↑,
HO-1↑,
Fenton↑,

641-

EGCG,

Se,

Antioxidant effects of green tea

ROS↑, Concentration is a factor that could determine whether green tea polyphenols act as antioxidants or pro-oxidants. EGC and EGCG, both generate hydrogen peroxide at concentrations greater than 10 μM
H2O2↑, Adding milk to green tea decreases formation of hydrogen peroxide,
ROS⇅, Selenium could enhance anticancer activity of green tea [29], possibly by enhancing antioxidant activity [30, 31], or even its pro-oxidant activity [32].

2309-

EGCG,

Chemo,

Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts

in-vitro,

PC,

MIA PaCa-2

(20–100 μM) for 72 h

in-vitro,

Nor,

HPNE

in-vitro,

PC,

PANC1

in-vivo,

NA,

mice

TumCG↓, EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner
eff↑, and the growth inhibition effect was further enhanced under glucose deprivation conditions.
ROS↑, EGCG at 40 µM increased ROS levels by 1.4- and 1.6-fold in Panc-1 and MIA PaCa-2 cells, respectively
ECAR↓, EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase.
ChemoSen↑, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo.
selectivity↑, EGCG at 80 µM for 72 h had significantly less effect on the HPNE cells, reducing cell growth by only 24%
Glycolysis↓, EGCG Inhibits Glycolysis through Suppressing Rate-Limiting Enzymes. EGCG Plus Gemcitabine Further Inhibits Glycolysis
PFK↓, EGCG treatment reduced both the activity and expression levels of phosphofructokinase (PFK) and pyruvate kinase (PK) in Panc-1 and MIA PaCa-2 cells
PKA↓,
HK2∅, EGCG failed to reduce hexokinases II (HK2) and lactate dehydrogenase A (LDHA) protein expression levels
LDHA∅,
PFKP↓, EGCG reduced the levels of PFKP and PKM2 (p < 0.01 for both) in pancreatic tumor xenograft homogenates, obtained from mice treated with EGCG
PKM2↓,
H2O2↑, EGCG at 40 µM increased H2O2 levels by 1.5- and 1.9-fold in Panc-1 and MIA PaCa-2 cells
TumW↓, EGCG and gemcitabine, given as single agents, reduced tumor weight by 40% and 52%, respectively, compared to vehicle-treated controls (p < 0.05 and p < 0.01). In combination, EGCG plus gemcitabine reduced tumor weight by 67%,

2514-

H2,

Hydrogen: A Novel Option in Human Disease Treatment

Review,

NA,

*Inflam↓, Anti-Inflammatory Effect of H2
*IL1β↓, decrease the overexpression of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α
*IL6↓,
*IL8↓,
*IL10↓,
*TNF-α↓,
*ROS↓, . H2 can also downregulate ROS directly or as a regulator of a gas-mediated signal.
*HO-1↓, H2 can enhance the expression of the heme oxygenase-1 (HO-1) antioxidant by activating nuclear factor erythroid 2-related factor 2 (Nrf-2), an upstream regulating molecule of HO-1
*NRF2↑,
*ER Stress↓, hydrogen inhalation significantly reduced the ER stress-related protein and alleviated tissue damage in myocardial I/R injury a
H2O2↑, H2-induced ROS production can also be observed in cancer cells.

1918-

JG,

ROS -mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro

in-vitro,

Liver,

HepG2

1-30uM

in-vivo,

NA,

4mg/kg

mice were intraperitoneally injected with 10%
dimethyl sulfoxide (DMSO) or JG (4 mg/kg) every other day for ten
times in tota

TumCG↓, JG significantly inhibited tumor growth in vivo
TumCP↓, JG effectively inhibited cell proliferation and induced apoptosis through extrinsic pathways
Apoptosis↑,
TumAuto↑, JG treatment induced autophagy flux
AMPK↑, activiting the AMPK-mTOR signaling pathway
mTOR↑,
P53↑, JG enhanced p53 activation
H2O2↑, JG enhanced the generation of hydrogen peroxide (H2O2)
ROS↑, JG caused apoptosis and autophagy via activating the ROS-mediated p53 pathway in human liver cancer cells in vitro and in vivo
toxicity↝, a slight loss in body weight was observed after JG injection (Fig. 1D), suggesting that JG might has slight side effects.
p62↓, rmarkable decrease of p62 level was observed after 30uM JG treatment
DR5↑,
Casp8↑,
PARP↑,
cl‑Casp3↑,

5117-

JG,

https://pubmed.ncbi.nlm.nih.gov/31283929/

vitro+vivo,

Liver,

TumCG↓, Here, the present results showed that JG significantly inhibited tumor growth in vivo.
TumCP↓, JG effectively inhibited cell proliferation and induced apoptosis through extrinsic pathways.
Apoptosis↑,
TumAuto↑, We also observed that JG treatment induced autophagy flux via activiting the AMPK-mTOR signaling pathway.
AMPK↑,
mTOR↑,
P53↑, JG enhanced p53 activation by increasing down-regulation of ubiquitin-mediated degradation
H2O2↑, JG enhanced the generation of hydrogen peroxide (H2O2) and superoxide anion radical (O2• -).
ROS↑, JG caused apoptosis and autophagy via activating the ROS-mediated p53 pathway in human liver cancer cells in vitro and in vivo

3457-

MF,

Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis

Review,

Var,

Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

523-

MF,

MTX,

Extremely low-frequency magnetic fields significantly enhance the cytotoxicity of methotrexate and can reduce migration of cancer cell lines via transiently induced plasma membrane damage

in-vitro,

AML,

THP1

10uM(MTX), 0.1 and 0.6 μT

in-vitro,

NA,

PC12

pheocrmomocytoma (PC12) Pheochromocytoma is a type of tumor

in-vivo,

Cerv,

HeLa

H2O2↑, These results suggest that ELF MF stimulation facilitates H2O2-dependent cell death in cancer cells as its effect was enhanced nearly two-fold
TumCD↑, 1 μM MTX
CellMemb↑,
eff↑, ELF-MF enhance the effects of methotrexate on THP-1 and PC12 cells

2259-

MFrot,

MF,

Method and apparatus for oncomagnetic treatment

in-vitro,

GBM,

Oncomagnetic patent

MMP↓, Oncomagnetic patent Fig 2
Bcl-2↓,
BAX↑,
Bak↑,
Cyt‑c↑,
Casp3↑, caspase staining rises progressively until after 30 min most of the cells fluoresce positive for caspase, revealing activation of this enzyme
Casp9↑,
DNAdam↑,
ROS↑, applying the oscillating magnetic field to the tissue increases the production of reactive oxygen species (ROS )
lactateProd↑,
Apoptosis↑,
MPT↑, opening of the mitochondrial membrane permeability transition pore
*selectivity↑, repetitive magnetic stimulation has shown decreased apoptosis in non -cancerous cells .
eff↑, oncomagnetic therapy may be performed in conjunction with other forms of therapy such as with chemotherapy, other forms of radiative therapy, with drugs and prescriptions, etc
MMP↓, OMF which in turn produces rapidly fluctuating or sustained depolarizations of the mitochondrial membrane potential (MMP) in the tissue .
selectivity↑, Because normal cells have a larger amount of mitochondria, have lower demand for ATP, and are not under stress, disruption of electron flow and small amount of ROS formation and MMP depolarization does not trigger apoptosis
TCA?, decrease in Krebs cycle metabolites
H2O2↑, increase in peroxide levels in GBM cells following stimulation by the system 100 using a rotating magnet
eff↑, combine the administration of BHB , or acetoacetate , or free fatty acid, or branched chain amino acid, or cryptochrome agonist , or MGMT inhibitor, or DNA alkylating agent, or DNA methylating agent, and OMF as a more effective treatment of cancer
*antiOx↑, upregulation of antioxidant mechanisms due to the application of OMFs further protects non -cancerous cells from any ROS -mediated apoptosis
H2O2↑, The experiments showed rapid increases in the levels of superoxide and H2O2 in GBM cells
eff↓, To test whether cell death is caused by the OMF - induced increase in ROS , a potent antioxidant Trolox was used to counteract it, while measuring the decrease in GBM cell count due to 4 h exposure to OMF.
GSH/GSSG↓, GSH/GSSG ratio almost exactly half that seen in control cells
*toxicity∅, No Cytotoxic Effect in Normal Cells
OS↑, OMF -Induced Prolongation of Survival in a Mouse Xenograft Model of GBM

186-

MFrot,

MF,

Selective induction of rapid cytotoxic effect in glioblastoma cells by oscillating magnetic fields

in-vitro,

GBM,

GBM

 new device that generates oscillating magnetic fields (OMF) by rapid rotation of strong permanent magnets in specially designed patterns of frequency and timing

in-vitro,

Lung,

mt-ROS↑, Cytotoxic effects of OMF may be caused by an increase in ROS
Casp3↑, Cell death is associated with activation of caspase 3
selectivity↑, OMF induces highly selective cell death of patient derived GBM cells associated with activation of caspase 3, while leaving normal tissue cells undamaged
TumCD↑, Exposure to OMF causes cancer cell death
ETC↓, The underlying mechanism is a marked increase in ROS in the mitochondria, possibly in part through perturbation of the electron flow in the respiratory chain.
H2O2↑, Figure 6A shows rapid increases in the levels of superoxide and H 2 O 2 in GBM cells,
eff↓, we used the potent antioxidant Trolox to counteract it,
GSH↑, We tested whether GSH synthesis was upregulated as a feedback protective effect in response to OMF-induced increase in ROS. An examination of GSH levels showed that there was a 20% elevation in treated cells
MMP↓, underlying mechanism involves a marked increase in ROS, mitochondrial membrane depolarization, fragmentation of mitochondrial network and activation of caspase 3.

184-

MFrot,

MF,

Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells

in-vitro,

GBM,

GBM

 80mT pulsed

ROS↑, sOMF
mitResp↓, Inhibit Mitochondrial Respiration
mtDam↑, Produce Loss of Mitochondrial Integrity
Dose↝, Repeated intermittent sOMF was applied for 2 hours at a specific frequency, in the 200-300 Hz frequency range, with on-off epochs of 250 or 500 ms duration.
MMP?, ROS generation has been shown to be driven, in part, by elevated mitochondrial membrane chemiosmotic potential (ΔΨ) and ubiquinol (QH2)
OCR↓, Immediately after cessation of field rotation we observe a loss of mitochondrial integrity (labeled LMI), with a very rapid increase in O2 consumption
mt-H2O2↑, We have previously demonstrated that sOMF treatment of cells generates superoxide/hydrogen peroxide in the mitochondrial matrix
eff↓, we repeated the same experiment in the presence of Trolox, which protects thiols from ROS oxidation (47). sOMF treatment of RLM in State 3u pre-treated with Trolox (15 μM), show minimal inhibition,
SDH↓, SDH Inhibition by sOMF in State 3u RLM Is Caused by ROS Generation
Thiols↓, suggest that thiol oxidation in SDH may result from sOMF.
GSH↓, Glutathione in the mitochondrial matrix can provide some protection from ROS, but after solubilizing the mitochondria, this protection is lost and the SDH becomes more sensitive to sOMF.
TumCD↑, sOMF is highly effective at killing non-dividing GBM cell cultures,
Casp3↑, caspase-3 activation 1 h after sOMF
Casp7↑, rapid activation of caspase-3/7
MPT↑, OMF-treated cell that causes near simultaneous MPT, release of cytochrome c and other apoptosis-inducing factors, resulting in caspase-3/7 activation in these GBM cells.
Cyt‑c↑,
selectivity↑, differential sensitivity to sOMF of cancer cells over ‘normal’ cells becomes apparent. rapid increase in the reactive oxygen species (ROS) in the mitochondria to cytotoxic levels only in cancer cells, and not in normal human cortical neurons
GSH/GSSG↓, increasing GSSG/GSH ratio
ETC↓, completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM)

4954-

PEITC,

Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate

vitro+vivo,

Ovarian,

SKOV3

 5 μM

ROS↑, Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using β-phenylethyl isothiocyanate (PEITC).
GSH↓, malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output
selectivity↑, Our study showed that PEITC has a superior selectivity compared to cisplatin. The ability to preferentially kill malignant cells is a promising feature of PEITC.
mtDam↑, Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death.
TumCD↑,
OS↑, In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.
eff↑, Furthermore, because PEITC has low toxicity in nonmalignant cells and exhibits anticancer selectivity superior to cisplatin,
*toxicity↓,
H2O2↑, t ROS induced by PEITC were mainly DCF-DA-reactive species such as hydrogen peroxide (H2O2) and nitric oxide (NO)
NO↑,
eff↓, 5 μM PEITC significantly increased DAF-FM fluorescence, which was reversed by the antioxidant N-acetyl-L-cysteine (NAC) but not by the H2O2-scavenging enzyme catalase
GPx↓, 500 μM PEITC inhibited GPX by approximately 50% and 90%, respectively. These concentrations could be achieved intracellularly when cells were incubated with 5–10 μM PEITC.
Dose↝, Interestingly, incubation of cells with 5–10 μM PEITC led to a depletion of cellular GSH, which is in the mM range. The explanation for this stoichiometric discrepancy is that PEITC can be concentrated in the cells. A
eff↑, combination of PEITC with curcumin was effective, suggesting that combination of PEITC with other agents may enhance anticancer activity.

1953-

PL,

Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation

in-vitro,

Lung,

A549

in-vitro,

Nor,

WI38

ROS↑, Piperlongumine (PL), a natural electrophilic alkaloid bearing two α, β-unsaturated imides, is a promising anticancer molecule by targeting the stress response to reactive oxygen species (ROS).
selectivity↑, 15-fold selectivity toward A549 cells over normal WI-38 cells.
TrxR↓, selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation.
TumCCA↑, S-phase arrest
GSH?, PL-CL sharply decreased the GSH levels of A549 cells in a dose- and time-dependent fashion (Figure 5A) but barely changed the GSH levels of WI-38 cells
H2O2↑, significant accumulation of ROS (O2.- and H2O2)

2941-

PL,

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

in-vivo,

BC,

MDA-MB-231

mice

in-vitro,

OS,

U2OS

in-vitro,

BC,

MDA-MB-453

ROS↑, . Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death
Apoptosis↑,
selectivity↑, but it has little effect on either rapidly or slowly dividing primary normal cells
*ROS∅, In contrast, PL did not cause an increase in ROS levels in normal cells
GSH↓, lead to a decrease in GSH and an increase in GSSG levels in cancer cells
GSSG↑,
H2O2↑, we found that hydrogen peroxide and nitric oxide, but not superoxide anion, were among the ROS species induced by PL in cancer cells
NO↑,
Half-Life?, 0.8 hrs

2957-

PL,

Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKβ Suppression in Human Breast Cancer Cells

in-vitro,

BC,

MCF-7

10–40 μM

TumCP↓, We found that PL decreased MCF-7 cell proliferation and migration.
TumCMig↓,
TumCCA↑, PL induced G2/M phase cell cycle arrest.
ROS↑, PL induced intracellular reactive oxygen species (hydrogen peroxide) accumulation and glutathione depletion
H2O2↑,
GSH↓,
IKKα↓, PL-mediated inhibition of IKKβ expression decreased nuclear translocation of NF-κB p65.
NF-kB↓,
P21↑, PL significantly increased p21 mRNA levels.
eff↓, PL significantly decreased cellular GSH levels, while in cells pre-treated with NAC, the GSH levels were similar to those observed in control cells

3930-

PTS,

A Review of Pterostilbene Antioxidant Activity and Disease Modification

Review,

Var,

Review,

adrenal,

Review,

Stroke,

*BioAv↑, It has increased bioavailability in comparison to other stilbene compounds. pterostilbene was shown to have 80% bioavailability compared to 20% for resveratrol making it potentially advantageous as a therapeutic agent
*antiOx↑, Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits.
*neuroP↑, anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes.
*Inflam↓,
*ROS↓, pterostilbene reduces oxidative stress (OS) and production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and superoxide anion (O2 −), which are implicated in the initiation and pathogenesis of several disease processes
*H2O2↓,
*GSH↑, pterostilbene have shown increased expression of the antioxidants catalase, total glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD).
*GPx↑,
*GSR↑,
*SOD↑,
TumCG↓, pterostilbene inhibit breast cancer in vitro and in vivo
PTEN↑, rats fed the blueberry diet exhibited higher mammary branching, increased nuclear immunoreactivity of tumor suppressor phosphatase and tensin homolog deleted in chromosome 10 (PTEN)
HGF/c-Met↓, blueberry extract significantly decreased human-growth-factor (HGF-) induced activation of the PI3 K/AkT/NK-κB pathway, which is implicated in breast carcinogenesis
PI3K↓,
Akt↓,
NF-kB↓,
TumMeta↓, inhibited the metastatic potential of breast cancer cells in vitro by inhibiting HGF-induced cell migration and matrix metalloproteinase-(MMP-) 2 and MMP-9 activity.
MMP2↓,
MMP9↓,
Ki-67↓, blueberry extract produced smaller tumors with decreased expression of Ki-67, a marker of cell proliferation, and increased expression of caspase-3, an apoptosis marker
Casp3↑,
MMP↓, increased mitochondrial depolarization,
H2O2↑, pterostilbene treatment increased GPx antioxidant activity and the production of H2O2 and singlet oxygen indicating a mechanism of ROS-induced apoptosis
ROS↑,
ChemoSen↑, pterostilbene treatment produced a synergistic inhibitory effect when combined with the chemotherapy drug Tamoxifen, demonstrating clinical potential in the treatment of breast cancer
*cardioP↑, blueberries, and pterostilbene alike, exhibit protective effects against cardiovascular disease possibly due to induction of antioxidant enzymes.
*CDK2↓, Pterostilbene also produced downregulation of the cell-cycle mediators, cyclin-dependent kinase (CDK)-2, CDK-4, cyclin E, cyclin D1, retinoblastoma (Rb), and proliferative cell nuclear antigen (PCNA), all of which promote unchecked VSMC proliferation
*CDK4↓,
*cycE/CCNE↓,
*cycD1/CCND1↓,
*RB1↓,
*PCNA↓,
*CREB↑, The authors found that treatment with blueberry extract decreased dopamine- (DA-) induced upregulation of the oxidative mediators, CREB and pPKCγ, indicating a significant antioxidant effect
*GABA↑, blueberry-fed aged rats had significant improvements in GABA potentiation and increased GSH compared to aged controls
*memory↑, 1- or 2-month blueberry diet showed significantly higher object memory recognition compared to control rats
*IGF-1↑, supplementation with blueberry extract was shown to enhance hippocampal plasticity and increase levels of insulin-like growth factor (IGF-) 1, IGF-2, and ERK resulting in improved spatial memory
*ERK↑,
TIMP1↑, increased endogenous tissue inhibitors of metalloproteinases (TIMPs)
BAX↑, ↑Bax, ↑cytochrome C, ↑Smac/Diablo, ↑MnSOD
Cyt‑c↑,
Diablo↑,
SOD2↑,

904-

QC,

Antioxidant and prooxidant effects of quercetin on glyceraldehyde-3-phosphate dehydrogenase

Analysis,

NA,

ROS↑, Quercetin significantly increased oxidation of GAPDH observed in the presence of ferrous ions
H2O2↑,

910-

QC,

The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism

tumCV↓,
Apoptosis↑,
PI3k/Akt/mTOR↓, QUE induces cell death by inhibiting PI3K/Akt/mTOR and STAT3 pathways in PEL cells
Wnt/(β-catenin)↓, reducing β-catenin
MAPK↝,
ERK↝, ERK1/2
TumCCA↑, cell cycle arrest at the G1 phase
H2O2↑,
ROS↑,
TumAuto↑,
MMPs↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
P53↑,
Casp3↑,
Hif1a↓, by inactivating the Akt-mTOR pathway [64,74] and HIF-1α
cFLIP↓,
IL6↓, QUE decreased the release of interleukin-6 (IL-6) and IL-10
IL10↓,
lactateProd↓,
Glycolysis↓, It is suggested that QUE alters glucose metabolism by inhibiting monocarboxylate transporter (MCT) activity
PKM2↓,
GLUT1↓,
COX2↓,
VEGF↓,
OCR↓,
ECAR↓,
STAT3↓,
MMP2↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
MMP9:TIMP1↓,
mTOR↓,

3071-

RES,

Resveratrol and Its Anticancer Effects

Review,

Var,

chemoPv↑, In this review, the effects of resveratrol are emphasized on chemopreventive, therapeutic, and anticancer.
SIRT1↑, RSV can directly activate Sirt1 expression and induce autophagy independently or dependently on the mammalian target of rapamycin (mTOR)
Hif1a↓, RSV suppresses tumor angiogenesis by inhibiting HIF-1a and VEGF protein
VEGF↓,
STAT3↓, RSV effectively prevents cancer by inhibiting STAT3 expression
NF-kB↓, also has an inhibitory effect on antiapoptotic mediators such as NF-kB, COX-2, phosphatidylinositol 3-kinase (PI3K), and mTOR (52).
COX2↓,
PI3K↓,
mTOR↓,
NRF2↑, Activation of the Nrf2/antioxidant response element (ARE) pathway by endogenous or exogenous stimuli under normal physiological conditions has the potential to inhibit cancer and/or cancer cell survival, growth, and proliferation
NLRP3↓, RSV downregulates the NLRP3 gene by activating the Sirt1 protein, thereby inducing autophagy
H2O2↑, RSV mediates cytotoxicity in cancer cells by increasing intracellular hydrogen peroxide (H2O2) and oxidative stress levels that will cause cell death
ROS↑,
P53↑, RSV activates p53, increases the expression of PUMA and BAX
PUMA↑,
BAX↑,

1744-

RosA,

Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity

Review,

Var,

chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↑, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells

5038-

SAS,

Rad,

Sulfasalazine, an inhibitor of the cystine-glutamate antiporter, reduces DNA damage repair and enhances radiosensitivity in murine B16F10 melanoma

in-vivo,

Melanoma,

B16-F10

xCT↓, Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential.
ROS↑,
RadioS↓, radio-sensitizing effect of sulfasalazine using a B16F10 melanoma model.
GSH↓, Sulfasalazine decreased glutathione concentrations and resistance to H2O2 in B16F10 melanoma cells, but not in mouse embryonic fibroblasts.
selectivity↑,
DNArepair↓, It inhibited cellular DNA damage repair and prolonged cell cycle arrest after X-irradiation.
TumCCA↑,
H2O2↑, SAS decreases cellular GSH and increases H2O2 cytotoxicity in B16F10 cells
Dose↝, At lower SAS concentrations (10–100 μM), we did not observe any increase in intracellular ROS. At higher concentrations of SAS (800–1,000 μM), intracellular ROS increased approximately 2.3-fold in B16F10 cells

2410-

SIL,

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

in-vitro,

GBM,

U87MG

in-vitro,

GBM,

U251

in-vivo,

NA,

nude mice

TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo

2362-

SK,

RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide

in-vitro,

GBM,

U87MG

in-vivo,

GBM,

Rat C6 tumor xenograft in nude mice

in-vitro,

GBM,

U251

RIP1↑, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression
RIP3↑,
Glycolysis↓,
G6PD↓, shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2
HK2↓,
PKM2↓,
H2O2↑, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine
GSH↓,
ROS↑, It was documented that inhibition of HK II with its inhibitor 3-bromopyruvate or knockdown of its level resulted in accumulation of ROS

2202-

SK,

Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification

in-vitro,

Var,

Iron↑, After delivering into glutathione (GSH)-overexpressed tumor cells, FeShik will disassemble and release Fe2+ to induce cell death via ferroptosis.
Ferroptosis↑,
pH↝, GOx executes its catalytic activity to produce an acid environment and plenty of H2O2 for stimulating •OH generation via the Fenton reaction
H2O2↑,
ROS↑,
Fenton↑,
GSH↓, SRF will suppress the biosynthesis of GSH by inhibiting system Xc-, further deactivating the enzymatic activity of glutathione peroxidase 4 (GPX4).
GPx4↓,
lipid-P↑, Up-regulation of the oxidative stress level and down-regulation of GPX4 expression can dramatically accelerate the accumulation of lethal lipid peroxides, leading to ferroptosis amplification of tumor cells

4891-

Sper,

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Review,

Var,

Review,

AD,

TumCCA↑, Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth.
TumCP↓,
TumCG↓,
*Inflam↓, health improving effects, that includes remarkable anti-inflammatory effects
*antiOx↑, It is also a potent antioxidant, and reportedly improves the respiratory function
*neuroP↑, Dietary intake of spermidine reduces the risk of neurodegeneration, metabolic diseases, heart ailments, and cancer.
*cognitive↑, spermidine-induced autophagy slows the rate of cognitive decline due to its ability to clear amyloid-beta plaques in the brain
*Aβ↓,
*mitResp↑, Spermidine supplementation also enhances mitochondrial metabolism, and translational activity.
AntiCan↑, anticancer properties of spermidine are of particular interest as it is known to reduce the cancer-related mortality in humans
TumCD↑, in addition to impacting their discourse with the immune effectors that result in expediting the identification of tumor-associated antigens and eventually cancer cell death
TumAuto↑, Inhibition of acetyltransferase EP300 by spermidine is known to induce autophagy, which is one of the desirable approaches in the treatment of cancer.
*AntiAge↑, Lifelong oral spermidine administration is reported to extend the lifespan in mice by 25%, as evidenced by genetic investigations.
LC3B-II↑, Western blotting experiments have showed a surge in the levels of LC3 II/LC3 I, Atg5, and Beclin 1 proteins in spermidine administered HeLa cells.
ATG5↑,
Beclin-1↑,
mt-ROS↑, Spermidine induces mitochondrial reactive oxygen species (mtROS) mediated M2-polarization by producing a surge in the levels of H2O2 and mitochondrial peroxide in the presence of spermidine.
H2O2↑,
Apoptosis↑, Spermine is known to induce apoptosis in primary human cells as well as the malignant tumor cells by producing a surge in the intracellular level of reactive oxygen species (ROS)
*ROS↑,
ChemoSen↑, A combination of 5-fluorouracil and spermine analogues N 1 , N 11 -diethylnorspermine (DENSPM) (6, Figure 5) at concentrations 1.25, 2.5, 5, and 10 μM or α-difluoromethylornithine (DFMO) led to a synergistic killing of HCT116 colon carcinoma cells
MMP↓, and loss of membrane potential of mitochondria followed by a subsequent release of cytochrome c
Cyt‑c↑,

5904-

TV,

Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development

Review,

Var,

Review,

Stroke,

Review,

Diabetic,

Review,

Obesity,

Review,

AD,

Review,

Arthritis,

*antiOx↑, shown to possess various pharmacological properties including antioxidant, free radical scavenging, anti-inflammatory, analgesic, antispasmodic, antibacterial, antifungal, antiseptic and antitumor activities.
*ROS↓,
*Inflam↓,
*Bacteria↓,
AntiTum↑,
IronCh↑, chelation of metal ions
*HDL↑, antihyperlipidemic (via increasing the levels of high density lipoprotein cholesterol and decreasing the levels of low density lipoprotein cholesterol
*LDL↓,
*BioAv↝, videnced the presence of thymol in the stomach, intestine, and urine after its oral administration with sesame oil at a dose around 500 mg in rats and 1–3 g in rabbits.
*Half-Life↝, Oral administration of a single dose of thymol (50 mg/kg) was rapidly absorbed and slowly eliminated approximately within 24 h.The maximum concentration (Tmax) was reached after 30 min, while approximately 0.3 h was needed for the half-life
*BioAv↑, The rapid absorption of thymol indicates that it’s mainly absorbed in the upper component of the gut
*SOD↑, scavenging of free radicals by increasing the activities of several endogenous antioxidant enzymes levels viz. superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST)
*GPx↑,
*GSTs↑,
*eff↑, Thymol (0.02–0.20%) showed better antioxidant capacity than its isomer carvacrol in lipid systems due to its greater steric hindrance
radioP↑, Owing to its potent antioxidant potential, thymol showed radioprotective and anticlastogenic potential in gamma radiation induced Swiss albino mice
*MDA↓, Thymol supplementation increased the antioxidant status and decreased malondialdehyde (MDA) levels in broiler chickens
*other↑, Dietary supplementation with the combination of carvacrol–thymol (1:1) (100 mg/kg) reduced the occurrence of oxidative stress and the impairment of the intestinal barrier in weaning piglets by its potent antioxidant property
*COX1↓, by inhibiting both isoforms of cyclooxygenase (COX), with the most active being against COX-1 with an IC50 value of 0.2 μM.
*COX2↓,
*AntiAg↑, Thymol (1.1 μg/ml) exhibited inhibitory effects against arachidonic-acid-induced blood coagulation and platelet aggregation in vitro
*RNS↓, Thymol inhibited ROS (IC50= 3 μg/ml), reactive nitrogen species (RNS) (IC50= 4.7) and significantly reduced generation of NO and H2O2 as well as activities of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide reduced oxidase (NADH oxi
*NO↓,
*H2O2↓,
*NOS2↓,
*NADH↓,
*Imm↑, Thymol (25–200 mg/kg) was shown to modulate the immune system in cyclosporine-A treated Swiss albino mice by enhancing the expressions of cluster of differentiation 4 (CD4),
Apoptosis↑, anticancer actions of thymol include induction of apoptosis, anti-proliferation, inhibition of angiogenesis and migration
TumCP↓,
angioG↓,
TumCMig↓,
Ca+2↑, Intracellular Ca2+ overload
TumCCA↑, Cytotoxicity by stimulating cell cycle arrest in G0/G1 phase
DNAdam↑, DNA fragmentation, Bax protein expression, activation of caspase -9, -8 and -3 & concomitant PARP cleavage, AIF translocation
BAX↑,
Casp9↑,
Casp8↑,
Casp3↑,
cl‑PARP↑,
AIF↑,
i-ROS↑, intracellular ROS, depolarizing MMP, cytochrome-c release, cleavage of caspases, DNA fragmentation, activation of apaf-1,
MMP↓,
Cyt‑c↑,
APAF1↑,
Ca+2↑, In human glioblastoma cells, thymol (200–600 μM) produced a rise in (Ca2+)i levels
MMP9↓, diminished matrix metallopeptidase-9 (MMP9) and matrix metallopeptidase-2 (MMP2) production as well as protein kinase Cα (PKCα) and extracellular signal-regulated kinases (ERK1/2) phosphorylation
MMP2↓,
PKCδ↓,
ERK↓,
H2O2↑, Thymol increased the production of ROS and mitochondrial H2O2 thereby depolarizing mitochondrial membrane potential.
BAX↑, up-regulating Bcl-2 associated X protein (Bax) expression and down-regulating B-cell lymphoma (Bcl-2)
Bcl-2↓,
DNAdam↑, Thymol (IC50= 497 and 266 mM) was shown to induce DNA damage by increasing the levels of lipid peroxidation products;
lipid-P↑,
ChemoSen↑, This study recommended the combination of thymol with various chemotherapeutic agents to minimize its toxicity on normal cells and to improve the effectiveness of cancer treatment
chemoP↑,
*cardioP↑, significant increase in the activities of heart mitochondrial antioxidants (SOD, catalase, GPx, GSH)
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*BP↓, Thymol (1, 3, and 10 mg/kg) administration decreased the blood pressure and heart rate of Wistar rats whereas thymol (5 mg/kg) attenuated blood pressure in rabbits
*AntiDiabetic↑, protective effects of thymol in metabolic disorders such as diabetes mellitus and obesity
*Obesity↓,
RenoP↑, Thymol (20 mg/kg) was shown to inhibit cisplatin-induced renal injury by attenuating oxidative stress, inflammation and apoptosis in male adult Swiss Albino rats
*GastroP↑, This gastroprotective effect of thymol is believed to be due to increased mucus secretion
hepatoP↑, Thymol (150 mg/kg) showed to inhibit paracetamol induced hepatotoxicity in mice by preventing the alterations in the activities of hepatic marker enzymes
*AChE↓, Thymol (EC50= 0.74 mg/mL) was shown to possess acetylcholine esterase inhibitory activity but much less than its isomer carvacrol
*cognitive↑, Thymol (0.5–2 mg/kg) has been shown to inhibit cognitive impairments caused by increased Aβ levels or cholinergic hypofunction in Aβ
*BChE↓, whereas thymol (100 and 1000 μg/ml) also inhibited both AChE and butyrylcholinesterase (BChE) in a dose dependent manner
*other↓, Thymol (100 mg/kg) was shown to inhibit collagen induced arthritis by decreasing lipid peroxidation mediated oxidative stress by increasing the status of antioxidants in male Wistar rats
*BioAv↑, The encapsulation of thymol into methylcellulose microspheres by spray drying remarkably increases the bioavailability compared to free thymol

4468-

VitC,

SSE,

Selenium modulates cancer cell response to pharmacologic ascorbate

in-vivo,

GBM,

U87MG

in-vitro,

CRC,

HCT116

eff↓, In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts
TumCD↑, pharmacologic ascorbate raises the serum ascorbate concentration into the millimolar range, a concentration at which ascorbate has been shown to kill cancer cells in vitro
ChemoSen↑, Pharmacologic ascorbate has been shown to synergize with multiple chemotherapeutic agents in animal models and is well-tolerated in human patients [1,4], motivating ongoing clinical trials.
ROS⇅, Indeed, the role of ascorbate as either a pro- or anti-oxidant has been suggested to depend on concentration, with low doses mitigating ROS and high doses generating them
DNAdam↑, H2O2 generation by ascorbate has been associated with DNA damage and subsequent PARP activation, which can deplete NAD and thereby inhibit glycolysis
PARP↑,
NAD↓,
Glycolysis↓,
Fenton↑, Ascorbate cytotoxicity depends on the intracellular labile iron pool (Fig 1a) [3,9]. One explanation for this phenomenon is that ascorbate-generated H2O2 causes toxicity through Fenton chemistry
lipid-P↑, extensive lipid peroxidation
eff↓, More generally, they establish dietary selenium depletion as a potential means of sensitizing tumors to free radical stress.
H2O2↑, High concentrations (mM) of ascorbate have been shown to generate H2O2 in vitro
other↝, Selenium supplementation has been shown to protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress

613-

VitC,

High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced Cancer

Review,

NA,

typ<5mM

H2O2↑,

612-

VitC,

VitK3,

Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action

H2O2↑,

610-

VitC,

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues

in-vitro,

lymphoma,

JPL119

0.5 mM

in-vitro,

BC,

MCF-7

2.5mM

in-vitro,

BC,

MDA-MB-231

7 mM

in-vitro,

BC,

HS587T

20 mM

in-vitro,

Nor,

>25 mM not known

not harm to normal cell ****  insensitive to 20 mM ascorbate

Apoptosis↑, ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
necrosis↑,
H2O2↑,
*toxicity↓, pharmacologic concentrations of ascorbate killed cancer but not normal cells All tested normal cells were insensitive to 20 mM ascorbate.

606-

VitC,

Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer

Review,

NA,

ROS↑, millimolar (mM) concentrations, also functions as a pro-oxidant
H2O2↑,
Fenton↑, elevated copper concentrations ... made cancer cells vulnerable to the ROS-generated selective cytotoxicity of copper and ascorbic acid

599-

VitC,

Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment

Review,

NA,

H2O2↑,
DNAdam↑,
ROS↑,
Fenton↑,
Apoptosis↑, Moderate concentrations of H2O2 typically induce apoptosis
necrosis↑, higher H2O2 concentrations induce necrosis

598-

VitC,

Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly

Review,

NA,

1g/kg over 90–120 minutes two to three times weekly is well tolerated

H2O2↑,
ROS↑,
TET1↑, DNA demethylation mediated by ten-eleven translocation enzyme activation
DNAdam↑,
G6PD∅, **** patients who receive intravenous ascorbate must be prescreened for glucose 6 phosphate dehydrogenase deficiency

Showing Research Papers: 1 to 50 of 57
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 57

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 2, GPx↑, 3, GPx1↑, 1, GPx4↑, 1, GSH↑, 3, GSR↑, 1, GSTs↑, 1, H2O2↓, 2, H2O2↑, 2, HDL↑, 1, HO-1↓, 1, HO-1↑, 1, MDA↓, 2, NADH↓, 1, NRF2↑, 2, RNS↓, 1, ROS↓, 4, ROS↑, 1, ROS∅, 1, SOD↑, 4, SOD1↑, 1,

Mitochondria & Bioenergetics ⓘ

mitResp↑, 1,

Core Metabolism/Glycolysis ⓘ

CREB↑, 1, LDL↓, 1,

Cell Death ⓘ

JNK↓, 1,

Transcription & Epigenetics ⓘ

other↓, 1, other↑, 1,

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,

DNA Damage & Repair ⓘ

PCNA↓, 1,

Cell Cycle & Senescence ⓘ

CDK2↓, 1, CDK4↓, 1, cycD1/CCND1↓, 1, cycE/CCNE↓, 1, RB1↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1, ERK↑, 1, IGF-1↑, 1, TCF-4↓, 1,

Migration ⓘ

AntiAg↑, 1, β-catenin/ZEB1↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

GastroP↑, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 1, IL10↓, 1, IL1β↓, 1, IL6↓, 1, IL8↓, 1, Imm↑, 1, Inflam↓, 4, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, BChE↓, 1, GABA↑, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↑, 4, BioAv↝, 1, eff↑, 2, Half-Life↝, 1, selectivity↑, 1,

Clinical Biomarkers ⓘ

BP↓, 1, IL6↓, 1, NOS2↓, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, AntiDiabetic↑, 1, cardioP↑, 2, CardioT↓, 1, cognitive↑, 2, memory↑, 1, neuroP↑, 2, Obesity↓, 1, toxicity?, 2, toxicity↓, 2, toxicity↝, 1, toxicity∅, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 77

Scientific Paper Hit Count for: H2O2, Hydrogen peroxide (H2O2)

15 Vitamin C (Ascorbic Acid)
5 EGCG (Epigallocatechin Gallate)
5 Magnetic Fields
3 Magnetic Field Rotating
3 Piperlongumine
3 VitK3,menadione
2 Silver-NanoParticles
2 Ajoene (compound of Garlic)
2 Baicalein
2 Selenium
2 Copper and Cu NanoParticles
2 Juglone
2 Quercetin
2 Shikonin
1 3-bromopyruvate
1 Alpha-Lipoic-Acid
1 Catechins
1 Chrysin
1 Citric Acid
1 chemodynamic therapy
1 Dichloroacetate
1 diet FMD Fasting Mimicking Diet
1 Chemotherapy
1 Hydrogen Gas
1 methotrexate
1 Phenethyl isothiocyanate
1 Pterostilbene
1 Resveratrol
1 Rosmarinic acid
1 Sulfasalazine
1 Radiotherapy/Radiation
1 Silymarin (Milk Thistle) silibinin
1 Spermidine
1 Thymol-Thymus vulgaris
1 Selenite (Sodium)
1 diet Short Term Fasting
1 glucose deprivation

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#:138  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

H2O2 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 ⓘ

Cellular Microenvironment ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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