NO Cancer Research Results

NO, Nitric Oxide: Click to Expand ⟱

Source:

Type:

Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment.
Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS).

– In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer.

• Expression Patterns in Tumors:
– Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment.

– Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.

Scientific Papers found: Click to Expand⟱

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↑,

4363-

AgNPs,

Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma

in-vivo,

fibroS,

particles was approximately 10 nm

LACA mice

TumVol↓, incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA
TNF-α↓, TNF-α, IL-6 and IL-1β these cytokines were found to be downregulated after treatment with AgNP-MSA
IL6↓,
IL1β↓,
*toxicity↝, liver sections were found to have normal architecture in all treated groups except those treated at the 9 and 10 mg/kg b.w. doses
TumCG↓, treatment with AgNPs, the logistic growth of the tumor incidence was significantly lower (
selectivity↑, MSA-AgNPs aggregated instantly in response to the acidic extracellular pH of solid tumors, leading to greatly enhanced uptake by cancer cells
selectivity↑, Because the particle size in the study was approximately 10 nm, any AgNP that escaped entry into the tumor microenvironment and entered the systemic circulation was effectively cleared from the body.
Weight↑, AgNP-MSA not only inhibited the tumor incidence but also helped to overcome the progressive body weight loss of tumor-bearing mice.
ROS↑, anticancer property demonstrated by AgNP can be attributed to this increase in oxidative stress in the tumor microenvironment.
NO↑, AgNPs significantly increased the oxygen free radical and NO levels in the tumor microenvironment, which oppose hypoxia.

4558-

AgNPs,

Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

in-vitro,

PC,

PANC1

3.19 ug/mL

ROS↑, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy.
selectivity↑, We found that the increase was lower in noncancer cells.
NO↑, PANC-1 cells with 0.5–5 μg/mL of 2.6 nm AgNPs or 5–100 μg/mL of 18 nm AgNPs caused an increase of NO level in a concentration-dependent manner
SOD↓, We observed a significant reduction in cytosolic and mitochondrial SOD and GPX-4 at protein level
GPx4↓,
Catalase↓, we showed that 2.6 nm AgNPs caused a higher decrease in SOD1, SOD2, and CAT at mRNA level after 24 h incubation than 18 nm AgNPs
TumCCA↑, 2.6 nm and 18 nm AgNPs, we noticed a decrease of G0/G1 phase cell population in a concentration-dependent manner compared with control
MMP↓, increase of the percentage of cells with low mitochondrial membrane potential (Δψm), compared to the untreated cells

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↓,

2776-

Bos,

Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities

Review,

Var,

*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)

1448-

Bos,

A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells

in-vitro,

AML,

HL-60

12ug/ml

TumCP↓,
Apoptosis↑,
ROS↑, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation
NO↑,
cl‑Bcl-2↑,
BAX↑, translocation of Bax to mitochondria
MMP↓, loss of mitochondrial membrane potential
Cyt‑c↑, release of cytochrome c to the cytosol
AIF↑, release to the cytosol
Diablo↑, release to the cytosol
survivin↓,
ICAD↓,
Casp↑,
cl‑PARP↑,
DR4↑,
TNFR 1↑,

1603-

Cu,

BP,

SDT,

Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response

in-vitro,

BC,

4T1

in-vivo,

NA,

mice

GSH↓, Cu2O was incorporated into BP(black phosphorus) to exhaust the overexpressed intracellular GSH
Fenton↑, However, the Cu+-catalyzed Fenton reaction converts H2O2 into OH at a high reaction rate, even in a neutral environment (160 times than that of Fe2+)
ROS↑, BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation,
NO↑,
sonoS↑, Numerous studies have confirmed that BP, as a sonosensitizer, can induce ROS generation in cancer therapy
eff↑, These results indicated that an acidic environment can effectively promote Cu release.
NO↑, massive NO production
*toxicity∅, Additionally, no significant body weight loss or apparent histological abnormalities of the major organs (heart, liver, spleen, lungs, and kidneys) were observed, indicating the negligible organ toxicity
eff?, In vivo studies demonstrated that BCL plus US treatment could significantly inhibit tumor growth

6050-

CUR,

SeNPs,

Efficacy of curcumin-selenium nanoemulsion in alleviating oxidative damage induced by aluminum chloride in a rat model of Alzheimer's disease

in-vivo,

AD,

rat

*cognitive↑, Treatment with a curcumin-selenium nanoemulsion has been shown to enhance behavioural performance and mitigate degenerative changes induced by aluminium chloride (AlCl3)
*AChE↓, This nanoemulsion also reduced the activity of acetylcholinesterase (AChE) and lowered levels of key proteins, including Aβ, p53, tau, nuclear factor erythroid 2-related factor 2 (Nrf2), and tumour necrosis factor-alpha (TNF-α).
*Aβ↓,
*P53↓,
*tau↓,
*NRF2↓,
*TNF-α↓,
*NO↑, it significantly decreased nitric oxide (NO) levels in the brain while enhancing the activity of catalase (CAT) and superoxide dismutase (SOD).
*Catalase↑,
*antiOx↑, The study highlights the antioxidant and anti-inflammatory properties of the curcumin-selenium nanoemulsion, suggesting its potential as a therapeutic option for alleviating AD induced by AlCl3.
*Inflam↓,

466-

CUR,

Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of hydroxycarboxylic acid receptor-1

in-vitro,

Liver,

HepG2

5 and 10 μM, 24 h

in-vitro,

Liver,

HuT78

GlucoseCon↓,
lactateProd↓,
pH↑,
NO↑,
LAR↓,
Hif1a↓, gene and protein
LDHA↓,
MCT1↓,
MDR1↓,
STAT3↓,
HCAR1↓,

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

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↑,

2861-

FIS,

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Review,

Nor,

Review,

Stroke,

Review,

Park,

*antiOx↑, Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS
*ROS↓, The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders.
*neuroP↑,
*NO↑, inhibits NO production.
BioAv↝, oral bioavailability of fisetin was reported 7.8 and 31.7% for oral doses of 100 and 200 mg/kg, respectively
*BBB↑, BBB permeability, fisetin can also affect hippocampal synaptic plasticity indirectly through the peripheral system
*toxicity↑, Furthermore, it did not show signs of toxicity at doses up to 2 g/kg in an acute toxicity study with no toxicity in the histopathological analysis of the heart, lungs, kidneys, liver, stomach, intestines, spleen and reproductive organs
*eff↑, potential benefits against neurological health complications and neurodegenerative diseases like AD, PD. HD, ALS, vascular dementia, schizophrenia, stroke, depression, diabetic neuropathy and traumatic brain injury
*GSH↑, direct antioxidant activity in addition to increasing intracellular antioxidants such as glutathione
*SOD↑, fig 2
*Aβ↓,
*12LOX↓,
*COX2↓,
*Catalase↑, Fisetin treatment prevented behavioral deficits, increased brain antioxidant, superoxide dismutase, catalase, reduced glutathione, and BDNF
*Inflam↓, decreased serum homocysteine, and pro-inflammatory biomarkers (TNF-α, IL-6), lipid peroxidation
*TNF-α↓,
*IL6↑,
*lipid-P↓,
NF-kB↓, suppressed the up-regulation of NF-κB, and IDO-1 genes expression, and decreased the rise of IL-1β levels.
IL1β↓,
NRF2↑, fisetin treatment also restored the downregulation of Nrf-2, HO-1, and ChAT genes expression and BDNF levels in the hippocampus, suggesting its protective effect against oxidative stress
HO-1↑,
GSTs↑, Fisetin also restored the AlCl3-induced reduction in the levels of SOD, CAT, GST, and GSH in a study that analysed the effect of this compound on AlCl3-induced reactive gliosis and neuronal inflammation in the brain of mice
cognitive↑, Fisetin improves neurodegenerative disease-associated dementia, cognitive functions and behavioral abnormalities along with increasing age
*BDNF↑, Fisetin also increases BDNF activity to prevent neurodegeneration

2825-

FIS,

Exploring the molecular targets of dietary flavonoid fisetin in cancer

Review,

Var,

*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
*p‑cMyc↑,
*NRF2↑,
*GSH↑,
*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
PI3K↓,
Akt↓,
TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
p27↑,
JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
MMP2↓,
MMP9↓,
uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
cFos↓,
cJun↓,
E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
Vim↓,
N-cadherin↓,
EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
Cyt‑c↑,
Diablo↑,
Casp↑,
cl‑PARP↑,
P53↑, fisetin with induction of p53 protein
COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
PGE2↓,
HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
HSP27↓,
DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
Casp3↑,
Casp9↑,
ROS↑, This was associated with production of intracellular ROS
AMPK↑, Fisetin induced AMPK signaling
NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
Ca+2↑,
mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
p70S6↓,
ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
IRE1↑,
ATF4↑,
GRP78/BiP↑,
eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h.

4028-

FulvicA,

Mineral pitch induces apoptosis and inhibits proliferation via modulating reactive oxygen species in hepatic cancer cells

in-vitro,

Liver,

HUH7

Apoptosis↑, MP enhanced anti-cancer effects by inducing apoptosis and inhibiting proliferation.
TumCP↓,
ROS↑, MP induced both ROS and NO, upon neutralizing them, there was a partial recovery of apoptosis and proliferation.
NO↑,
Dose↝, MP is a humic matter, shown to contain fulvic acid and humic acid, which are responsible for its biochemical activities.
MMP↓, mitochondrial membrane potential is reduced, cytochrome c is released, the transition pores are opened and calcium is released by the increased NO level which eventually leads to apoptosis
Cyt‑c↑,
SOD↓, SOD activity in Huh-7 cells was found to be decreasing with increasing concentrations of MP
Catalase↓, catalase activity was significantly decreased in all the concentrations of MP that was tested.
GSH↑, Glutathione production was significantly increased with the increasing concentrations of MP. There was a more than 7-fold increase of glutathione production with 100, 500 and 1000 μg/ml of MP
lipid-P↑, lipid peroxidation of the cancer cells was found to be increased in concentration dependent manner.
miR-21↓, MP induces ROS and nitric oxide, enhances the expression of miRNA-22 and decreases the expression of miRNA-21, a known onco-miR.
miR-22↑,

4343-

H2,

Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation

vitro+vivo,

NA,

*antiOx↑, H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.
*AntiAg↑,
*NO↑,
*ERK↑,

2238-

MF,

Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects

Review,

Var,

*BMD↑, Therapeutic bone-growth stimulation via Ca2+/nitric oxide/cGMP/protein kinase G. Multiple studies have implicated increased Ca2+ and nitric oxide in the EMF stimulation of bone growth
*VGCC↑, increased VGCC activity following EMF exposure and suggests, therefore, that VGCC stimulation in the plasma membrane is directly produced by EMF exposure.
*Ca+2↑, Other studies, each involving VGCCs, summarized in Table 1, also showed rapid Ca2+ increases following EMF exposure [8, 16, 17, 19, 21].
*NO↑, Multiple studies have implicated increased Ca2+ and nitric oxide in the EMF stimulation of bone growth
*eff↓, Voltage-gated calcium channel stimulation leads to increased intracellular Ca2+, which can act in turn to stimulate the two calcium/calmodulin-dependent nitric oxide synthases and increase nitric oxide.

4105-

MF,

Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases

Review,

AD,

*Inflam↓, On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset.
*neuroP↑, TMS (60 Hz, 0.7 mT) applied to rats for 2 hours twice daily, can be neuroprotective
*NO↑, The growth curve of exposed bacteria was lower than the control, while field application increased NO levels
*ROS↓, A significant increase of free radical production has been observed after exposure to 50 Hz electromagnetic fields at a flux density of 1 mT to mouse macrophages
*NO↓, EMF represents a non-pharmacological inhibitor of NO and an inducer of MCP-1,
*MCP1↑,
*HSP70/HSPA5↑, Tokalov and Gutzeit (2004) showed the effect of ELF-EMF on heat shock genes and demonstrated that even a low dose of ELF-EMF (10 mT) caused an increase in HSPs, especially hsp70
*antiOx↑, Whereas most environmental electromagnetic radiations cause oxidative stress in the brain (Sahin and Gumuslu, 2007), ELF-EMF seems to have an antioxidant and neuroprotective effect
*NRF2↑, ELF-EMF induces the antioxidant pathway Nrf2, which is closely associated with its protective effect against neurotoxicity induced by 3-nitropropionic acid (3-NP)
*NF-kB↓, Selective inhibition of the NF-κB signaling pathway by ELF-EMF may be involved in the decrease of chemokine production.

4111-

MF,

Coupling of pulsed electromagnetic fields (PEMF) therapy to molecular grounds of the cell

Review,

Arthritis,

*Inflam↓, ultimately lead to a dampening of inflammatory signals like interleukins
*Cartilage↑, this therapy has positive effects for the regeneration of musculoskeletal tissues such as cartilage, bone, tendon and ligament
*Pain↓, Ryang We et al. [18] found a significant beneficial effect of PEMF on WOMAC pain scores at 1 month compared with a sham treatment
*QoL↑, significant improvements in mobility, daily activity score as well as global score during treatment of acute osteoarthritis of knee joint
*Dose↝, PEMF stimulation (38 Hz, 2 mT) for 2 h per day enhanced osteoblastic functions through amelioration of the cytoskeletal organization;
*VEGF↑, increase of anti-inflammatory prostaglandins, and a huge rise in the Vascular Endothelial Growth Factor (VEGF)-A-mRNA transcription.
*NO↑, stimulatory effect of PEMF on osteoblast proliferation and differentiation is accompanied by an increase in nitric oxide (NO) synthesis
*TGF-β↑, Transforming Growth Factor (TGF-β) family is enhanced by PEMF[67] and local expression of TGF-β results in improved bone fracture healing
*MMP9↓, PEMF treatment suppressed IL-1β-mediated up-regulation of MMP-9 protein levels.
*PGE2↑, Sontag and Dertinger [97] investigated the liberation of prostaglandin E2 (PGE2) during application of EMF of different frequencies: here “windows” at 6 and 16 Hz were found, where PGE was 200% above 0 Hz baseline.
*GPx3↑, PEMF exposure also induced expression of GPX3, SOD2, CAT and GSR on mRNA, protein and enzyme activity level
*SOD2↑,
*Catalase↑,
*GSR↑,
*Ca+2↑, many EMF-effect studies is a direct action on voltage-gated calcium channels (VGCCs) (Figure 1). This is normally accompanied by a rapid increase of Ca2+

4101-

MF,

Benign Effect of Extremely Low-Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Human,

Stroke,

40 Hz, 7 mT, for 15 min/day

Forty-eight patients

*motorD↑, ELF-EMF treatments improved functional and mental status
*cognitive↑,
*eff↑, We conclude that ELF-EMF therapy is capable of promoting recovery in poststroke patients.
*NO↑, evidence that application of extremely low-frequency electromagnetic field increases nitric oxide generation and its metabolism, as well as improving the effectiveness of poststroke ischemic patients' treatments.
*other↝, Due to its vasodilating and proangiogenic effects, NO serves as a protective function during cerebral ischemia
*neuroP↑, In conclusion, ELF-EMF therapy increases the metabolism and generation of NO, which has both neuroprotective and cytotoxic properties.

3477-

MF,

Electromagnetic fields regulate calcium-mediated cell fate of stem cells: osteogenesis, chondrogenesis and apoptosis

Review,

NA,

*Ca+2↑, When cells are subjected to external mechanical stimulation, voltage-gated ion channels in the cell membrane open and intracellular calcium ion concentration rises
*VEGF↑, BMSCs EMF combined with VEGF promote osteogenesis and angiogenesis
*angioG↑,
Ca+2↑, 1 Hz/100 mT MC4-L2 breast cancer cells EMF lead to calcium ion overload and ROS increased, resulting in necroptosis
ROS↑,
Necroptosis↑,
TumCCA↑, 50 Hz/4.5 mT 786-O cells ELF-EMF induce G0/G1 arrest and apoptosis in cells lines
Apoptosis↑,
*ATP↑, causing the ATP or ADP increases, and the purinergic signal can upregulate the expression of P2Y1 receptors
*FAK↑, Our research team [53] found that ELE-EMF can induce calcium oscillations in bone marrow stem cells, up-regulated calcium ion activates FAK pathway, cytoskeleton enhancement, and migration ability of stem cells in vitro is enhanced.
*Wnt↑, ability of EMF to activate the Wnt10b/β-catenin signaling pathway to promote osteogenic differentiation of cells depends on the functional integrity of primary cilia in osteoblasts.
*β-catenin/ZEB1↑,
*ROS↑, we hypothesize that the electromagnetic field-mediated calcium ion oscillations, which causes a small amount of ROS production in mitochondria, regulates the chondrogenic differentiation of cells, but further studies are needed
p38↑, RF-EMF was able to suppress tumor stem cells by activating the CAMKII/p38 MAPK signaling pathway after inducing calcium ion oscillation and by inhibiting the β-catenin/HMGA2 signaling pathway
MAPK↑,
β-catenin/ZEB1↓,
CSCs↓, Interestingly, the effect of electromagnetic fields is not limited to tumor stem cells, but also inhibits the proliferation and development of tumor cells
TumCP↓,
ROS↑, breast cancer cell lines exposed to ELE-EMF for 24 h showed a significant increase in intracellular ROS expression and an increased sensitivity to further radiotherapy
RadioS↑,
Ca+2↑, after exposure to higher intensity EMF radiation, showed a significant increase in intracellular calcium ion and reactive oxygen species, which eventually led to necroptosis
eff↓, while this programmed necrosis of tumor cells was able to be antagonized by the calcium blocker verapamil or the free radical scavenger n -acetylcysteine
NO↑, EMF can regulate multiple ions in cells, and calcium ion play a key role [92, 130], calcium ion acts as a second messenger that can activate downstream molecules such as NO, ROS

229-

MFrot,

MF,

Molecular mechanism of effect of rotating constant magnetic field on organisms

in-vivo,

Nor,

New Zealand rabbits, rotating constant magnetic field on organisms

*NO↑, lasted 3hrs
*5HT↓, 5-HT content in mice brain decreased significantly after the treatment of RCMF
*eff↝, 5-HT content reached the lowest point after magnetic field treatment for 90 min and 60 min in decortex brain and small intestine respectively, but it returned to the normal level after two hours
*eff↝, inhibition of magnetic field on vomiting reaction was parallel to the decreasing level of 5-HT content in brain and small intestine tissue
*β-Endo↑, After animals and voluntary patients were treated by magnetic field, their plasma β-endorphin increased 23 times higher than before.
*other↓, Under the action of magnetic field, the synthesis and secretion of melatonin are weakened in pineal gland, and the melatonin content decreases in plasma

1666-

PBG,

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

Review,

Var,

ChemoSen↑, Ingredients from propolis also ”sensitize“ cancer cells to chemotherapeutic agents
TumCCA↑, cell-cycle arrest and attenuation of cancer cells proliferation
TumCP↓,
Apoptosis↑,
antiOx↓, behave as antioxidants against peroxyl and hydroxyl radicals,
ROS↑, whereas prooxidant activity is observed in the presence of Cu2+.
COX2↑, Propolis, as well as flavonoids derived from propolis, such as galangin, is a potent COX-2 inhibitor
ER(estro)↓, Some flavonoids from propolis, such as galangin, genistein, baicalein, hesperetin, naringenin, and quercetin, suppressed the proliferation of an estrogen receptor (ER)
cycA1/CCNA1↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
CycB/CCNB1↓,
CDK2↓,
P21↑,
p27↑,
hTERT/TERT↓, leukemia cells, propolis successfully reduced hTERT mRNA expression
HDAC↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
ROS⇅, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
Dose?, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
ROS↓, By scavenging free radicals, chelating metal ions (mainly iron and copper), and stimulating endogenous antioxidant defenses, propolis and its flavonoids directly attenuate the generation of ROS
ROS↑, Romanian propolis [99], exhibits prooxidant properties at high concentrations, by mobilizing endogenous copper ions and DNA-associated copper in cells.
DNAdam↑, propolis, i.e., its polyphenolic components, may induce DNA damage in the presence of transition metal ions.
ChemoSen↑, Algerian propolis + doxorubicin decreased cell viability, prevented cell proliferation and cell cycle progression, induced apoptosis by activating caspase-3 and -9 activities, and increased the accumulation of chemotherapeutic drugs in MDA-MB-231 cel
LOX1↓, propolis components inhibited the LOX pathway
lipid-P↓, Croatian propolis improved psoriatic-like skin lesions induced by irritant agents n-hexyl salicylate or di-n-propyl disulfide by decreasing the extent of lipid peroxidation
NO↑, Taken together, propolis may increase the phagocytic index, NO production, and production of IgG antibodies
Igs↑,
NK cell↑, propolis treatment for 3 days increases the cytotoxic activity of NK cells against murine lymphoma.
MMPs↓, extracts of propolis containing artepillin C and CAPE decreased the formation of new vessels and expression of MMPs and VEGF in various cancer cells
VEGF↓,
Hif1a↓, Brazilian green propolis inhibit the expression of the hypoxia-inducible factor-1 (HIF-1) protein and HIF-1 downstream targets such as glucose transporter 1, hexokinase 2, and VEGF-A
GLUT1↓,
HK2↓,
selectivity↑, Portuguese propolis was selectively toxic against malignant cells.
RadioS↑, propolis increased the lifespan of mice that received the radiotherapy with gamma rays
GlucoseCon↓, Portuguese propolis disturbed the glycolytic metabolism of human colorectal cancer cells, as evidenced by a decrease in glucose consumption and lactate production
lactateProd↓,
eff↓, Furthermore, different pesticides or heavy metals can be found in propolis, which can cause unwanted side effects.
*BioAv↓, Due to the low bioavailability and clinical efficacy of propolis and its flavonoids, their biomedical applications remain limited.

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.

4944-

PEITC,

Phenethyl isothiocyanate induces DNA damage-associated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations

in-vitro,

Oral,

TumCG↓, PEITC was able to inhibit cell growth, arrest G2/M phase, and induce apoptosis of OSCC cells.
TumCCA↑, PEITC-induced G2/M phase arrest and apoptosis depend on the GSH redox stress- and p53-related pathway
Apoptosis↑,
ROS↑, PEITC induced reactive oxygen species and NO production, GSH depletion, and ΔΨm reduction in OSCC cells.
NO↑,
GSH↓,
MMP↓,
DNAdam↑, PEITC-induced oxidative DNA damage was associated with the activation of the ATM–Chk2–p53 pathway.
ATM↑,
Chk2↑,
P53↑,
eff↓, Pifithrin-α, NAC, or GSH, but not free radical scavengers, can reverse anticancer effects of PEITC.

1947-

PL,

Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer

in-vitro,

GC,

SGC-7901

in-vitro,

GC,

TrxR1↓, In vivo, PL treatment markedly reduces the TrxR1 activity and tumor cell burden
ROS↑, PL may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells
ER Stress↑, PL induces a lethal endoplasmic reticulum stress and mitochondrial dysfunction in human gastric cancer cells
mtDam↑,
selectivity↑, known to selectively kill tumor cells while sparing their normal counterparts. PL treatment did not cause a significant increase in ROS levels in normal GES-1 cells
NO↑, we found that nitric oxide was also induced by PL in gastric cancer cells
TumCCA↑, PL treatment significantly induced G2/M cell cycle arrest in human gastric cancer SGC-7901, BGC-823 and KATO III cells.
mt-ROS↑, mitochondrial ROS, were involved in the PL-induced cell death in gastric cancer cells.
Casp9↑, Notably, caspase-9 activity was significantly elevated after PL treatment in SGC-7901 cells
Bcl-2↓, PL treatment dose-dependently decreased the expression of antiapoptotic proteins Bcl-2 and Bcl-xL, but induced the cleavage of poly (ADP-ribose) polymerase (PARP)
Bcl-xL↓,
cl‑PARP↑,
eff↓, Pre-incubation with GSH attenuated these effects confirming their linkage to PL-induced oxidative stress
lipid-P↑, PL dose-dependently increased the level of lipid peroxidation product (MDA), a marker of ROS, in tumor tissues

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

2445-

SFN,

Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

SkBr3

TumCCA↑, SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence
P21↑,
p27↑,
NO↑, effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling
Akt↓,
ATP↓, decreased pools of ATP and AMPK activation, and autophagy induction
AMPK↑,
TumAuto↑,
DNMT1↓, decreased levels of DNA methyltransferases (DNMT1, DNMT3B)
HK2↓, A decrease in HK2 levels was observed in SFN-treated MDA-MB-231 cells
PKM2↓, and a decrease in PKM2 levels was noticed in SFN-treated MDA-MB-231 and SK-BR-3 cells
HDAC3↓, . In contrast, HDAC3 , HDAC4 , HDAC6 , HDAC7 , HDAC8 ), HDAC9 and HDAC10 (histone deacetylase 10) mRNA levels were decreased in SFN-treated MDA-MB-231 cells
HDAC4↓,
HDAC8↓,

1937-

TQ,

Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

NA,

Nor,

3T3

3-12uM

*ROS↓, In this study, TQ-NLC or TQ was seen to reduce the level of ROS produced in the cells at all concentrations of treatment given.
*antiOx↓, Both of these compounds are able to exert their antioxidant activity at the concentration as lower as 3 μM within 24 hours of treatment and as higher as 12 μM without causing any harm towards the cells.
*BioAv↓, bioavailability of TQ is limited by its poor solubility and lipophilic nature in water
*BioAv↑, to overcome the disadvantages of TQ, thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was designed and effectively prepared by Ng et al. [49] via high-pressure homogenization technique
*NO↑, TQ was also reported to decrease production of nitric oxide (NO) and attenuate nitrosative stress by inhibiting the inducible nitric oxide synthase enzyme
*SOD↑, TQ exhibits strong antioxidant activity by upregulating superoxide dismutase (SOD), glutathione (GPX), and catalase (CAT) [88].
*GPx↑,
*Catalase↑,

1928-

TQ,

Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

TumCP↓, TQ+TRAIL significantly inhibited the protein content-based proliferation of MDA-MB-231 cells more than MCF-7 cells.
DR4↑, synergistic effect of them significantly up-regulated the genetic expressions of DR4, DR5, Cas-8, and FADD genes
DR5↑,
Casp8↑,
FADD↑,
Bcl-2↓, inhibited the genetic expression of the Bcl-2
ROS↑, The induction of the apoptotic genes using the combined therapy was stimulated by the elevation of the reactive oxygen species (ROS); nitric oxide (NO) and malondialdehyde (MDA) levels.
NO↑,
MDA↑,

2350-

UA,

Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells

in-vitro,

BC,

MCF-7

20uM

in-vitro,

BC,

MDA-MB-231

Akt↓, UA (20 µM) also diminished AKT signaling that affected glycolysis as judged by decreased levels of HK2, PKM2, ATP and lactate.
Glycolysis↓,
HK2↓,
PKM2↓,
ATP↓, 20 µM UA caused a decrease in intracellular ATP and lactate pools
lactateProd↓,
AMPK↑, UA-induced energy stress activated AMPK that resulted in cytotoxic autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
ERK↓, UA-promoted apoptosis was associated with decreased pERK1/2 signals and the depolarization of mitochondrial membrane potential.
MMP↓,
NO↑, 20 µM UA treatment resulted in an increase in nitric oxide levels
ROS↑, UA-induced elevation in total reactive oxygen species (ROS), total superoxide and mitochondrial superoxide production was more potent than BA-mediated oxidative stress
DNAdam↑, UA and BA promoted DNA breaks,

2411-

UA,

Ursolic acid in health and disease

Review,

Var,

Inflam↓, UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects
antiOx↑,
NF-kB↓, Colon cancer HCT116, HT29 20 μM for 8 hour ↓ NF-kB, Bcl-xL, Bcl-2, and cyclin D1
Bcl-xL↓,
Bcl-2↓,
cycD1/CCND1↓,
Ki-67↓, ↓ Ki67, CD31, STAT3, and EGFR, ↑ p53 and p21 mRNA expression
CD31↓,
STAT3↓,
EGFR↓,
P53↑,
P21↓,
HK2↓, MCF-7, MDA-MB-231 20 μM for 24 hours ↓ HK2, PKM2, ATP, and lactate ↓ pERK1/2, and depolarization of mitochondrial membrane potential, ↑ Nitric oxide and ATM
PKM2↓,
ATP↓,
lactateProd↓,
p‑ERK↓,
MMP↓,
NO↑,
ATM↑,
Casp3↑, T24 cancer cells ↑ Caspase 3 activity ↑ AMPK activation ↑ JNK activation
AMPK↑,
JNK↑,
FAO↑, 80 μM UA reduces triglyceride (TG) and cholesterol levels by increasing fatty acid oxidation and decreasing fatty acid synthesis in hepatocytes
FASN↓,
*GSH↑, ↑ Vitamin C, E, GSH, SOD, CAT, GPx, GST, and GR in heart
*SOD↑,
*Catalase↑,
*GPx↑,
*GSTs↑,
neuroP↑, This demonstrates that UA has a protective effect against various inflammatory conditions of the brain.

Showing Research Papers: 1 to 31 of 31

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 31

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 2, antiOx↑, 5, Catalase↑, 6, GPx↑, 2, GPx3↑, 1, GSH↓, 1, GSH↑, 3, GSR↑, 1, GSTs↑, 1, HO-1↑, 1, lipid-P↓, 1, MDA↓, 1, NRF2↓, 1, NRF2↑, 2, ROS↓, 5, ROS↑, 1, ROS∅, 1, SOD↑, 5, SOD2↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1, p‑cMyc↑, 1,

Cell Death ⓘ

iNOS↓, 1, p‑JNK↓, 1, p38↓, 1,

Transcription & Epigenetics ⓘ

other↓, 1, other↝, 1,

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,

DNA Damage & Repair ⓘ

P53↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 2, VGCC↑, 1, Wnt↑, 1,

Migration ⓘ

5LO↓, 1, AntiAg↑, 1, Ca+2↑, 3, Cartilage↑, 1, FAK↑, 1, MMP11↑, 1, MMP3↓, 1, MMP3↑, 1, MMP9↓, 1, TGF-β↑, 1, β-catenin/ZEB1↑, 1, β-Endo↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1, NO↓, 2, NO↑, 12, VEGF↑, 2,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 2, IL1β↓, 1, IL6↓, 1, IL6↑, 1, Inflam↓, 6, MCP1↑, 1, NF-kB↓, 1, PGE2↓, 1, PGE2↑, 2, Th1 response↓, 1, Th2↑, 2, TNF-α↓, 3, TNF-α↑, 1,

Synaptic & Neurotransmission ⓘ

5HT↓, 1, AChE↓, 1, BDNF↑, 1, tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↑, 1, Dose↝, 1, eff↓, 1, eff↑, 2, eff↝, 2,

Clinical Biomarkers ⓘ

BMD↑, 1, IL6↓, 1, IL6↑, 1,

Functional Outcomes ⓘ

cognitive↑, 3, memory↑, 1, motorD↑, 1, neuroP↑, 3, Pain↓, 1, QoL↑, 1, toxicity↓, 1, toxicity↑, 1, toxicity↝, 1, toxicity∅, 1,
Total Targets: 87

Scientific Paper Hit Count for: NO, Nitric Oxide

6 Magnetic Fields
4 Silver-NanoParticles
3 Curcumin
2 Boswellia (frankincense)
2 Fisetin
2 Phenethyl isothiocyanate
2 Piperlongumine
2 Thymoquinone
2 Ursolic acid
1 Copper and Cu NanoParticles
1 Black phosphorus
1 SonoDynamic Therapy UltraSound
1 Selenium NanoParticles
1 EGCG (Epigallocatechin Gallate)
1 Shilajit/Fulvic Acid
1 Hydrogen Gas
1 Magnetic Field Rotating
1 Propolis -bee glue
1 Sulforaphane (mainly Broccoli)

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

NO Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

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 ⓘ

Hormonal & Nuclear Receptors ⓘ

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 ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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