NF-kB Cancer Research Results

NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
5147- AgNPs,    Size dependent anti-invasiveness of silver nanoparticles in lung cancer cells
- in-vitro, Lung, A549
TumCMig↓, 13 nm AgNPs significantly inhibit the migration and invasiveness of lung adenocarcinoma A549 cells, induce elevated reactive oxygen species and lead to NF-κB directed cellular apoptosis
TumCI↓,
ROS↑,
p‑NF-kB↑, 13 nm AgNPs was able to significantly upregulate the phosphorylation of NF-κB (p-NF-κB) in A549 cells
selectivity↑, we speculate that, AgNPs, which are pointed out that have a sustained release of Ag+ in an environment with lower pH (such as cancer cells)
eff↝, and this inhibitive effect is most pronounced treated with 13 nm AgNPs, while the effect starts decreasing with the size of 45 nm and completely vanishes for 92 nm AgNPs.

356- AgNPs,  MF,    Anticancer and antibacterial potentials induced post short-term exposure to electromagnetic field and silver nanoparticles and related pathological and genetic alterations: in vitro study
- in-vitro, BC, MCF-7 - in-vitro, Bladder, HTB-22
Apoptosis↑,
P53↑, Up-regulation in the expression level of p53, iNOS and NF-kB genes as well as down-regulation of Bcl-2 and miRNA-125b genes were detected post treatment.
iNOS↑,
NF-kB↑,
Bcl-2↓,
ROS↑, the present study evaluated the levels of ROS as well as the antioxidant enzymes (SOD and CAT)
SOD↑,
TumCCA↑, S phase arrest and accumulation of cells in G2/M phase was observed following exposure to AgNPs and EMF, respectively.
eff↑, Apoptosis induction was obvious following exposure to either ELF-EMF or AgNPs, however their apoptotic potential was intensified when applied in combination
Catalase↑, Catalase (CAT)
other↑, swollen cells, swollen nuclei with mixed euchromatin and heterochromatin, ruptured cell membranes

402- AgNPs,  MF,    Anticancer and antibacterial potentials induced post short-term exposure to electromagnetic field and silver nanoparticles and related pathological and genetic alterations: in vitro study
- in-vitro, BC, MCF-7
P53↑,
iNOS↑,
NF-kB↑,
Bcl-2↓,
miR-125b↓,
ROS↑, 2.9x for 2hr
SOD↑, 2.4x for 2hr

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

5356- AL,    Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
- Review, GC, NA
Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

298- ALA,  Rad,    Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
- in-vitro, BC, MDA-MB-231
Apoptosis↑,
P53↑,
p38↑,
NF-kB↑, NF-κB were significantly increased in the ALA+RT group compared to the control
TumCCA↑, G2/M cell cycle arrest.

1123- aLinA,    Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A
- in-vitro, BC, NA - in-vitro, NA, MCF10
TumCP↑, Linoleic acid (LA) induces proliferation and invasion in breast cancer cells.
E-cadherin↓,
Snail↑, increase of Snail1, Snail2, Twist1, Twist2 and Sip1 expressions.
Twist↑,
ZEB2↑,
FAK↑,
NF-kB↑,
MMP2↓, Furthermore, LA induces FAK and NFκB activation, MMP-2 and -9 secretions, migration and invasion.
MMP9↓,
*EMT↑, LA promotes an EMT-like process in MCF10A
TumCI↑,

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

874- B-Gluc,    Potential promising anticancer applications of β-glucans: a review
- Review, NA, NA
AntiCan↑,
TumCG↓, reduced the tumor progression in S180 tumor-bearing mice
BAX↑, β-(1-3)-glucan has increased the Bax expression and decreased the Bcl-2 expression, which leads to apoptosis in S180 tumor-bearing mice.
Bcl-2↓,
IFN-γ↑, soluble β-glucan of low molecular weight enhanced IFN-γ production more efficiently than particle β-glucan of high molecular weight
PI3K/Akt↑, The binding of β-glucans to dectin-1 activates several signaling pathways such as PI3K/Akt, MAPK, NFAT, and NF-κB that result in ROS production, phagocytosis, and cytokine secretion
MAPK↑,
NFAT↑,
NF-kB↑,
ROS↑,
NK cell↑, β-glucans specifically activate and enhance the function of NK cells
TumCCA↑, Some β-glucans significantly induce the cell cycle arrest in the G1-phase due to the restriction of ERK1/2 or the ERK5 pathway, while others induce a gradual dose-dependent accumulation of cells at the G2/M phase along with a decrease in the populat
ERK↓, restricting the activity of the ERK1/2 pathway
Telomerase↓, β-glucans can also induce apoptosis by inhibiting the telomerase activity

5505- Ba,    Baicalein inhibits the progression of thyroid cancer by suppressing the TPL2/MEK2/ERK2 pathway
- in-vitro, Thyroid, NA
ERK↓, BA has also anti-tumor effects on TC, inhibiting the ERK1/2 and PI3K/Akt pathways to induce the apoptosis and autophagy in TC cells (16, 17)
PI3K↓,
Akt↓,
Apoptosis↑,
TumAuto↑,
NF-kB↑, Our previous research suggested that BA activates the NF-κB signaling pathway to induce the autophagy and apoptosis
MEK↓, BA modulates PLAU expression via inhibiting TPL2/MEK2/ERK2 pathway to regulate Golgi apparatus reprogramming

5551- BBM,    Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis
- vitro+vivo, Bladder, NA
tumCV↓, our results showed that berbamine inhibited cell viability, colony formation, and proliferation.
TumCP↓,
TumCCA↑, Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression
P21↑,
p27↑,
cycD1/CCND1↓, as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression.
cycA1/CCNA1↓,
CDK2↓,
EMT↓, In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis.
TumMeta↓,
p65↓, Mechanistically, the expression of P65, P-P65, and P-IκBα was decreased upon berbamine treatment
p‑p65↓,
IKKα↓,
NF-kB↑, berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-κB pathway.
ROS↑, More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1.
NRF2↓,
HO-1↓,
SOD2↓,
GPx1↓,
Bax:Bcl2↑, increase in the ratio of Bax/Bcl-2.
TumVol↓, berbamine successfully inhibited tumor growth and blocked the NF-κB pathway in our xenograft model

5582- BetA,    Targeting mitochondrial apoptosis by betulinic acid in human cancers
- Review, Var, NA
Apoptosis↑, BA has been reported to induce apoptosis via a direct effect on mitochondria.
MMP↓, BA triggered loss of mitochondrial membrane potential
Cyt‑c↑, BA was shown to trigger cytochrome c in a permeability transition pore-dependent
ROS↑, Generation of ROS upon treatment with BA has been reported to be involved in initiating mitochondrial membrane permeabilization [15].
NF-kB↑, These findings indicate that the activation of NF-kB by BA promotes BA-induced apoptosis in a cell type- specific manner.
angioG↓, antiangiogenic activity of BA was linked to its mitochondrial damaging effects [33]
mtDam↑,
TOP1↓, BA can inhibit the catalytic activity of topoisomerase I
selectivity↑, normal cells of different origin have been reported to be much more resistant to BA than cancer cells pointing to some tumor selectivity [19,25,44,45].
ChemoSen↑, his suggests that BA can be used as a sensitizer in combination regimens to enhance the efficacy of anticancer therapy or to bypass some forms of drug resistance
TumCG↓, BA also suppressed tumor growth in several animal models of human cancer.
chemoPv↑, BA has also been reported to act as a chemopreventive agent.
RadioS↑, BA may also be used in combination protocols to enhance its antitumor activity, for example with chemo- or radiotherapy or with the death receptor ligand TRAIL. B

2722- BetA,    Betulinic Acid for Cancer Treatment and Prevention
- Review, Var, NA
MMP↓, betulinic acid induced loss of mitochondrial membrane potential
Cyt‑c↑, betulinic acid was shown to trigger cytochrome c
cl‑Casp3↑, Cleavage of caspase-3 and -8 was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species.
cl‑Casp8↑,
ROS↑,
NF-kB↑, Betulinic acid was identified as a potent activator of NF-κB in a number of cancer cell lines
TOP1↓, betulinic acid was shown to inhibit the catalytic activity of topoisomerase I

2728- BetA,    Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy
- in-vitro, Var, NA
NF-kB↑, BetA activates NF-kappaB in a variety of tumor cell lines.
IKKα↑, BetA-induced NF-kappaB activation involved increased IKK activity
eff↓, NF-kappaB inhibitors in combination with BetA would have no therapeutic benefit or could even be contraproductive in certain tumors, which has important implications for the design of BetA-based combination protocols.

2729- BetA,    Betulinic acid in the treatment of tumour diseases: Application and research progress
- Review, Var, NA
ChemoSen↑, Betulinic acid can increase the sensitivity of cancer cells to other chemotherapy drugs
mt-ROS↑, BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress
STAT3↓, inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways.
NF-kB↓,
selectivity↑, A main advantage of BA and its derivatives is that they are cytotoxic to different human tumour cells, while cytotoxicity is much lower in normal cells.
*toxicity↓, It can kill cancer cells but has no obvious effect on normal cells and is also nontoxic to other organs in xenograft mice at a dose of 500 mg/kg
eff↑, BA combined with chemotherapy drugs, such as platinum and mithramycin A, can induce apoptosis in tumour cells
GRP78/BiP↑, In animal xenograft tumour models, BA enhanced the expression of glucose-regulated protein 78 (GRP78)
MMP2↓, reduced the levels of matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, in lung metastatic lesions of breast cancer, indicating that BA can reduce the invasiveness of breast cancer in vivo and block epithelial mesenchymal transformation (EMT
P90RSK↓,
TumCI↓,
EMT↓,
MALAT1↓, MALAT1, a lncRNA, was downregulated in hepatocellular carcinoma (HCC) cells treated with BA in vivo,
Glycolysis↓, Suppressing aerobic glycolysis of cancer cells by GRP78/β-Catenin/c-Myc signalling pathways
AMPK↑, activating AMPK signaling pathway
Sp1/3/4↓, inhibiting Sp1. BA at 20 mg/kg/d, the tumour volume and weight were significantly reduced, and the expression levels of Sp1, Sp3, and Sp4 in tumour tissues were lower than those in control mouse tissues
Hif1a↓, Suppressing the hypoxia-induced accumulation of HIF-1α and expression of HIF target genes
angioG↓, PC3: Having anti-angiogenesis effect
NF-kB↑, LNCaP, DU145 — Inducing apoptosis and NF-κB pathway
NF-kB↓, U266 — Inhibiting NF-κB pathway.
MMP↓, BA produces ROS and reduces mitochondrial membrane potential; the mitochondrial permeability transition pore of the mitochondrial membrane plays an important role in apoptosis signal transduction.
Cyt‑c↑, Mitochondria release cytochrome C and increase the levels of Caspase-9 and Caspase-3, inducing cell apoptosis.
Casp9↑,
Casp3↑,
RadioS↑, BA could be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.
PERK↑, BA treatment increased the activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptosis pathway and decreased the expression of Sp1.
CHOP↑,
*toxicity↓, BA at a concentration of 50 μg/ml did not inhibit the growth of normal peripheral blood lymphocytes, indicating that the toxicity of BA was at least 1000 times less than that of doxorubicin

2752- BetA,    Betulinic acid: a natural product with anticancer activity
- Review, Var, NA
selectivity↑, nontransformed cells of different origin, e.g., fibroblasts, melanocytes, neuronal cells and peripheral blood lymphocytes, have been reported to be much more resistant to the cytotoxic effect of BA than cancer cells
ChemoSen↑, BA was found to cooperate with various chemotherapeutic drugs, including doxorubicin, etoposide, cisplatin, taxol, and actinomycin D, to induce apoptosis and to inhibit clonogenic survival of tumor cells
RadioS↑, These reports suggest that using BetA as sensitizer in chemotherapy-, radiotherapy-, or TRAIL-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy.
MMP↓, BA directly induces loss of mitochondrial membrane potenti
cl‑Casp3↑, BA, induced cleavage of both caspases-8 and -3 in cytosolic extracts.
Cyt‑c↑, cytochrome c, released from mitochondria undergoing BA-mediated permeability transition, activated caspase-3 but not caspase-8 in a cell-free system.
ROS↑, Cleavage of caspases-3 and -8 was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species (ROS).
NF-kB↑, BA is a potent activator of NF-kB in a variety of tumor cell lines.
TOP1↓, BA blocks the catalytic activity of topoisomerase I by abrogating the inter- action of the enzyme and the DNA substrate

5650- BNL,    Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model
- in-vivo, Nor, NA
*P-gp↓, Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression.
*NF-kB↑, Borneol could activate nuclear factor-κB (NF-κB)
*eff↓, inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol.
*Dose↝, Moreover, 10 μg/mL and 20 μg/mL borneol treatment decreased P-gp expression in BMECs, the reduction of P-gp expression were 27% and 58% compared to control group respectively at 4 h after treatment

2772- Bos,    Mechanistic role of boswellic acids in Alzheimer’s disease: Emphasis on anti-inflammatory properties
- Review, AD, NA
*neuroP↑, (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD
*Inflam↓,
*AChE↓, inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels
*Choline↑,
*NRF2↑, BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD
*NF-kB↑,
*BBB↑, AKBA has efficiently abled to cross the blood brain barrier (BBB)
*BioAv↑, bioavailability of AKBA was significantly higher in case of sublingual route when compared to intranasal administration, as demonstrated by area under curves (AUCs) analysis
*Half-Life↓, half-life of the drug was about six hours and peak plasma levels of the drug reach 30 hrs after oral administration of 333 mg of BSE.
*Dose↝, drug needs to be administered at a dosing interval of 6 hrs
*PGE2↓, BAs possessed anti-inflammatory activity by inhibiting microsomal prostaglandin E2 synthase-1 (mPGES1)
*ROS↓, prevented oxidative stress-induced neuronal damage and cognitive impairment because of the antioxidant, anti-inflammatory and anti-glutamatergic effects
*cognitive↑,
*antiOx↑,
5LO↓, AKBA significantly reduced pro-inflammatory mediators such as 5-LOX, TNF-α, IL-6 levels and improve cognition
*TNF-α↓,
*IL6↓,
*HO-1↑, AKBA shows neuroprotective effects against ischaemic injury via nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade activation

4263- CA,    Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action
- Review, AD, NA
*neuroP↑, neuroprotective effect of CA on neuronal cells subjected to ischemia/hypoxia injury via the scavenging or reduction of ROS (reactive oxygen species) and NO (nitric oxide) and inhibition of COX-2 and MAPK pathways
*ROS↓,
*NO↓,
*COX2↓,
*MAPK↓,
*NRF2↑, CA is known to activate the Keap1/Nrf2 pathway, thereby resulting in the production of cytoprotective proteins.
*GSH↑, activation of GSH metabolism
*HO-1↑, activation of Nrf2 target genes, including heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TXNRD1)
*5HT↑, Observations of increased serotonin and BDNF suggest that CA may represent a novel therapeutic avenue for depressive behaviors that should be further explored.
*BDNF↑, 10 μM CA results in a 1.5-fold increase in levels of BDNF
*PI3K↑, CA has been shown to mediate the activation of the PI3K/Akt/NF-κB pathway
*Akt↑,
*NF-kB↑,
*BBB↑, CA was shown to ameliorate brain edema and blood-brain barrier (BBB) disruption
*SIRT1↑, CA was also shown to increase SIRT1
*memory↑, CA was shown to significantly improve short-term and spatial memory attributes in rat models of AD
*Aβ↓, CA also delayed the deposition of Aβ and protected cells against Aβ-induced cholinergic and mitochondrial dysfunction in a Caenorhabditis elegans model of AD
*NLRP3↓, CA also inhibits the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, which plays a critical role in the pathogenesis of neurodegenerative disorders, including AD and PD and COVID-19

5959- CEL,    Celecoxib induces apoptosis in cervical cancer cells independent of cyclooxygenase using NF-κB as a possible target
- in-vitro, Cerv, HeLa
Apoptosis↑, Celecoxib induced apoptosis independent of COX-2 activity.
Casp8↑, This event accompanied the activation of caspase-8 and -9 with Bid cleavage and the loss of mitochondrial membrane potential.
Casp9↑,
cl‑BID↑,
MMP↓,
NF-kB↑, Celecoxib-induced apoptosis is associated with NF-κB activation.
Dose⇅, The chemopreventive effect of celecoxib was also achieved only at relatively high doses (400–800 mg daily) in a human clinical trial, but not at a therapeutic daily dose of 200 mg
chemoPv⇅,
COX2↓, less than 10 μM of celecoxib is needed to inhibit the COX activity, while the concentrations required to inhibit tumor cell growth range from 30 μM to 100 μM

5986- Chit,    The natural product chitosan enhances the anti-tumor activity of natural killer cells by activating dendritic cells
- Study, Var, NA
NK cell↑, In this study, we discovered that chitosan enhanced the anti-tumor activity of natural killer (NK) cells by activating dendritic cells (DCs).
IFN-γ↑, In the presence of DCs, chitosan augmented IFN-γ production by human NK cells.
IL12↑, Mechanistically, chitosan activated DCs to express pro-inflammatory cytokines such as interleukin (IL)-12 and IL-15, which in turn activated the STAT4 and NF-κB signaling pathways, respectively, in NK cells.
IL15↑,
STAT4↑,
NF-kB↑, in NK cells
DCells↑, Collectively, our results demonstrate that chitosan activates DCs leading to enhanced capacity for immune surveillance by NK cells.

2783- CHr,    Apoptotic Effects of Chrysin in Human Cancer Cell Lines
- Review, Var, NA
TumCP↓, chrysin has shown to inhibit proliferation and induce apoptosis, and is more potent than other tested flavonoids in leukemia cells
Apoptosis↑,
Casp↑, chrysin is likely to act via activation of caspases and inactivation of Akt signaling in the cells.
PCNA↓, inhibited the growth of cervical cancer cells, HeLa, via apoptosis induction and down-regulated the proliferating cell nuclear antigen (PCNA) in the cells.
p38↑, chrysin potentially induced p38, therefore activated NFkappaB/p65 in the HeLa cells
NF-kB↑,
DNAdam↑, only apigenin, chrysin, quercetin, galangin, luteolin and fisetin were found to clearly induce the oligonucleosomal DNA fragmentation at 50 μM after 6 h of treatment
XIAP↓, down-regulation of X-linked inhibitor of apoptosis protein (XIAP) in the U937 cells
Cyt‑c↑, (1) chrysin mediated the release of cytochrome c from mitochondria into the cytoplasm;
Casp3↑, (2) chrysin induced elevated caspase-3 activity and proteolytic cleavage of its downstream targets, such as phospholipase C-gamma-1 (PLC-gamma1), which is correlated with down-regulation of XIAP;
Akt↓, (3) chrysin decreased phosphorylated Akt levels in cells where the PI3K pathway plays a role in regulating the mechanism.
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling by inhibiting the PI3K pathway
hTERT/TERT↓, A significant decrease in human telomerase reverse transcriptase (hTERT) expression levels was also observed in leukemia cells treated with 60 ng/mL Manisa propolis, owing to its constituent of chrysin
COX2↓, Chrysin also inhibited the lipopolysaccharide-induced COX-2 expression via inhibition of nuclear factor IL-6 (NF-IL6)
*Inflam↓, anti-inflammatory [21] and anti-oxidant effects [22], and has shown cancer chemopreventive activity via induction of apoptosis in diverse range of human and rat cell types.
*antiOx↑,
*chemoPv↑,
AR-V7?,
CYP19?, Chrysin has recently shown to be a potent inhibitor of aromatase [18] and of human immunodeficiency virus activation in models of latent infection

1085- DHA,  EPA,    DHA and EPA Down-regulate COX-2 Expression through Suppression of NF-kappaB Activity in LPS-treated Human Umbilical Vein Endothelial Cells
- in-vitro, Nor, HUVECs
*COX2↓, EPA, DHA, or troglitazone significantly reduced COX-2
*NF-kB↓, >10uM
*PGE2↓,
*IL6↓,
*NF-kB↑, low dose (10uM) significantly increased the activity of NF-κB

5008- DSF,  Cu,    Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis
- in-vitro, HCC, NA
selectivity↑, We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells
TumCD↑,
TumCMig↓,
TumCI↓,
angioG↓,
mtDam↑, Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death.
Iron↑,
lipid-P↑,
Ferroptosis↑,
NF-kB↑, Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu.
p‑p62↑, DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2.
Keap1↓,
eff↑, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis
eff↓, Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu.
ChemoSen↑, Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase.

3236- EGCG,  Buty,    Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate
- in-vitro, Colon, RKO - in-vitro, Colon, HCT116 - in-vitro, Colon, HT29
Apoptosis↑, combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells.
TumCCA?,
HDAC1↓, decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines.
DNMT1↓,
survivin↓,
HDAC↓,
P21↑, induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65.
NF-kB↑,
γH2AX↑, An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels
ac‑H3↑, induction of histone H3 hyperacetylation was also observed with combination treatment.
DNAdam↑,

2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
COX2↓, fisetin altered the expression of cyclooxygenase 2 (COX2) thereby suppressed the secretion of prostaglandin E2 ultimately resulting in the inhibition of epidermal growth factor receptor (EGFR) and NF-κB in human colon cancer cells HT29
PGE2↓,
EGFR↓,
Wnt↓, fisetin treatment inhibited the stimulation of Wnt signaling pathway via downregulating the expression of β-catenin and Tcell factor (TCF) 4
β-catenin/ZEB1↓,
TCF↑,
Apoptosis↑, fisetin triggers apoptosis in U266 cells through multiple pathways: enhancing the activation of caspase-3 and PARP cleavage, decreasing the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1 L ),
Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Mcl-1↓,
BAX↑, ncreasing the expression of pro-apoptotic proteins (Bax, Bim, and Bad)
BIM↑,
BAD↑,
Akt↓, decreasing the phosphorylation of AKT and mTOR and elevating the expression of acetyl CoA carboxylase (ACC
mTOR↓,
ACC↑,
Cyt‑c↑, release the cytochrome c and Smac/Diablo into the cytosol
Diablo↑,
cl‑Casp8↑, fisetin exhibited an increased level of cleaved caspase-8, Fas/Fas ligand, death receptor 5/TRAIL, and p53 levels in HCT-116 cells
Fas↑,
DR5↑,
TRAIL↑,
Securin↓, Securin gets degraded on exposure to fisetin in colon cancer cells.
CDC2↓, fisetin decreased the expression of cell division cycle proteins (CDC2 and CDC25C)
CDC25↓,
HSP70/HSPA5↓, Fisetin induced apoptosis as a result of the downregulation of HSP70 and BAG3 and the inhibition of Bcl-2, Bcl-x L and Mcl-1. T
CDK2↓, AGS 0, 25, 50, 75 μM – 24 and 48 h ↓CDK2, ↓CDK4, ↓cyclin D1, ↑casapse-3 cleavage
CDK4↓,
cycD1/CCND1↓,
MMP2↓, A549 0, 1, 5, 10 μM- 24 and 48 hr: ↓MMP-2, ↓u-PA, ↓NF- κB, ↓c-Fos, ↓c-Jun
uPA↓,
NF-kB↓,
cFos↓,
cJun↓,
MEK↓, ↓ MEK1/2 and ERK1/2 phosphorylation, ↓N-cadherin, ↓vimentin, ↓snail, ↓fibronectin, ↑E-cadherin, ↑desmoglein
p‑ERK↓,
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↓,
NF-kB↑, increased expression of NF-κB p65 leading to apoptosis was due to ROS generation on exposure to fisetin
ROS↑,
DNAdam↑, increased ROS triggered cell death through PARP cleavage, DNA damage and mitochondrial membrane depolarization.
MMP↓,
CHOP↑, Though fisetin upregulated CHOP expression and increased the production of ROS, these events fail to induce apoptosis in Caki cells.
eff↑, 50 μM fisetin + 1 mM melatonin Sk-mel-28 Enhances anti-tumour activity [54] 20 μM fisetin + 1 mM melatonin MeWo Enhances anti-tumour activity [54] 10 μM fisetin + 0.1 μM melatonin A549 Induces autophagic cell death
ChemoSen↑, 20 μM fisetin + 5 μM sorafenib A375, SK-MEL-28 Suppresses invasion and metastasis [44] 40 μM fisetin + 10 μM cisplatin A549, A549-CR Enhances apoptosis

2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
*neuroP↑, honokiol has neuroprotective effects.
*NF-kB↑, honokiol could reduce cytokine production and stimulate glial nuclear factor kappa B (NFκB) to eliminate the inflammatory response during cerebral ischemia-reperfusion activity
MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
BAX↑, BAX was increased, and the expression of Bcl-2 was suppressed in both honokiol-treated cells, indicating that honokiol induced apoptosis in the human glioma cell lines U87-MG and U251-MG.
Bcl-2↓,
antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2↓,
MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
CXCR4↓,
PI3K↓,
Akt↓,
ERK↓,
TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
LC3B-II↑,
EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
E-cadherin↑,
N-cadherin↓,
Wnt↓,
ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
iNOS↓, Luteolin in colon cancer and the complications associated with it, particularly the decreasing effect on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
COX2↓,
NRF2↑, Luteolin has been identified to increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial transcription factor with anticarcinogenic properties related
Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
ChemoSen↓, high dose of Luteolin application negatively affected the oxaliplatin-based chemotherapy in a p53-dependent manner [52]. They suggested that the flavonoids with Nrf2-activating ability might interfere with the chemotherapeutic efficacy of anticancer
IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
AR↓, downregulating the androgen receptor (AR) expression
TIMP1↑, Luteolin inhibits the migration of U251MG and U87MG human glioblastoma cell lines by downregulating MMP-2 and MMP-9 and upregulating the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2.
TIMP2↑,
ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
CDK2↓, Luteolin’s ability to decrease Akt, polo-like kinase 1 (PLK1), cyclin B1, cyclin A, CDC2, cyclin-dependent kinase 2 (CDK2) and Bcl-xL
Telomerase↓, Luteolin dose-dependently inhibited the telomerase levels and caused the phosphorylation of NF-κB and the target gene of NF-κB, c-Myc to suppress the human telomerase reverse transcriptase (hTERT)
p‑NF-kB↑,
p‑cMyc↑,
hTERT/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
MDR1↓,

4785- Lyco,    The Protective Anticancer Effect of Natural Lycopene Supercritical CO2 Watermelon Extracts in Adenocarcinoma Lung Cancer Cells
- in-vitro, Lung, A549
ROS↑, we found that Lyc W significantly increased the spontaneous release of ROS
NF-kB↑, We found that Lyc W significantly increased the nuclear expression of NF-kB in comparison to medium (p = 0.0289) and to Lyc G, Lyc T and Lyc S treatments
Apoptosis↑, Lyc W Induces Cell Apoptosis

1780- MEL,    Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing
- Review, Var, NA
*antiOx↑, Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy.
*toxicity↓,
ChemoSen↑,
*eff↑, melatonin was superior in preventing free radical destruction compared to other antioxidants, vitamin E, β-carotene, vitamin C, and garlic oil
*mitResp↑, increasing the expression and activity of the mitochondrial respiration chain complexes
*ATP↑, increasing the expression and activity of the mitochondrial respiration chain complexes
*ROS↓, most attractive property of melatonin is that its metabolites also regulate the mitochondrial redox status by scavenging ROS and RNS
*CardioT↓, melatonin has a protective effect on the heart without affecting DOX's antitumor activity,
*GSH↑, improving the de novo synthesis of glutathione (GSH) by promoting the activity of gamma-glutamylcysteine synthetase
*NOS2↓, melatonin inhibits the production of nitric oxide synthase (NOS)
*lipid-P↓, lipid peroxidation was reduced after melatonin treatment (role in induces organ failure)
eff↑, but it also enhances its antitumor activity more than vitamin E
*HO-1↑, melatonin upregulates heme oxygenase-1 (HO-1) (role in induces organ failure)
*NRF2↑, decreased bladder injury and apoptosis due to the upregulation of Nrf2 and nuclear transcription factor NF-κB expression
*NF-kB↑,
TumCP↓, significantly reduced cell proliferation
eff↑, Pretreatment with melatonin effectively preserved the ovaries from cisplatin-induced injury
neuroP↑, Melatonin has neuroprotective roles in oxaliplatin-induced peripheral neuropathy

1170- MushCha,    Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism
- in-vitro, Oral, HSC4
tumCV↓,
TumCP↓,
TumCCA↑,
STAT3↓,
Glycolysis↓,
MMP↓,
TumAuto↑,
p38↑, Chaga mushroom extract is likely to induce apoptosis via activation of p38 MAPK and NF-κB pathways.
NF-kB↑,

1668- PBG,    Propolis: A Detailed Insight of Its Anticancer Molecular Mechanisms
- Review, Var, NA
antiOx↑, Propolis has well-known therapeutic actions including antioxidative, antimicrobial, anti-inflammatory, and anticancer properties.
Inflam↓,
AntiCan↑,
TumCP↓, primarily by inhibiting cancer cell proliferation, inducing apoptosis
Apoptosis↑,
eff↝, Depending on the bee species, geographic location, plant species, and weather conditions, the chemical makeup of propolis fluctuates significantly
MMPs↓, via inhibiting the metastatic protein expression such as MMPs (matrix metalloproteinases)
TNF-α↓, inhibit inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-1/2 (COX ½), lipoxygenase (LOX), prostaglandins (PGs), and interleukin 1- β (IL1-β)
iNOS↓,
COX2↓,
IL1β↑,
*BioAv↓, Despite the low bioavailability of Artepillin C, a compound with a wide variety of physiological activities
BAX↑, Egyptian propolis extract revealed high apoptotic effects through an increase in BAX (pro-apoptotic protein), caspase-3, and cytochrome-c expression levels, and by a reduction in B-cell lymphoma2 (BCL2)
Casp3↑,
Cyt‑c↑,
Bcl-2↓,
eff↑, enhanced the G0/G1 cell cycle arrest induced by methotrexate
selectivity↑, Thailand propolis on normal and cancerous cells carried out by Umthong et al. found significant differences with the propolis showing cytotoxicity against cancerous but not normal cells.
P53↑, significant increases in the levels of p53 in cells treated with propolis extracts.
ROS↑, propolis induced apoptosis in the SW620 human colorectal cancer cell line through mitochondrial dysfunction caused by high production of reactive oxygen species (ROS) and caspase activation
Casp↑,
eff↑, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
ERK↓, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
Dose∅, propolis extracts at concentrations of 50 μg/mL significantly increased the levels of TRAIL in cervical tumor cell lines
TRAIL↑,
NF-kB↑, p53, NF-κB, and ROS. These molecules were found to be elevated following exposure of the cells to the alcoholic extract of the propolis
ROS↑,
Dose↑, high concentrations, propolis increased the amounts of integrin β4, ROS, and p53
MMP↓, high expression levels of these molecules, in turn, drove a decrease in mitochondrial membrane potential
DNAdam↑, propolis extract induced DNA fragmentation
TumAuto↑, CAPE, were found to induce autophagy in a breast cancer cell line (MDA-MB-231) through upregulating LC3-II and downregulating p62,
LC3II↑,
p62↓,
EGF↓, downregulation of EGF, HIF-1α, and VEGF
Hif1a↓,
VEGF↓,
TLR4↓, downregulating Toll-like receptor 4 (TLR-4), glycogen synthase kinase 3 beta (GSK3 β), and NF-κB signaling pathways
GSK‐3β↓,
NF-kB↓,
Telomerase↓, Propolis was shown to inhibit the telomerase reverse transcriptase activity in leukemia cells.
ChemoSen↑, Propolis has been shown to increase the activity of existing chemotherapeutic agents and inhibit some of their side effects
ChemoSideEff↓,

2950- PL,    Overview of piperlongumine analogues and their therapeutic potential
- Review, Var, NA
AntiAg↑, PL has been shown to exert in vitro antiplatelet aggregation effect induced by agonists such as collagen, adenosine 50-diphosphate (ADP), arachidonic acid (AA) and thrombin.
neuroP↑, Neuroprotective activity of PL and its derivatives
Inflam↓, Anti-inflammatory activity of PL and its derivatives
NO↓, production of NO and PGE2 was significantly inhibited after the treatment of PL.
PGE2↓,
MMP3↓, PL also significantly suppressed the production of MMP-3 and MMP-13
MMP13↓,
TumCMig↓, PL inhibited the proliferation, induced the apoptosis and reduced the migration and invasion of RA FLS by activating the p38, JNK, NF-kB and STAT3 pathways
TumCI↓,
p38↑,
JNK↑,
NF-kB↑,
ROS↑, PL has been reported to selectively induce apoptotic by ROS accumulation in cancer cells via different molecular mechanisms.
FOXM1↓, PL inhibited proteasome including suppression of FOXM1
TrxR1↓, induction of ROS by directly inhibiting thioredoxin reductase 1 (TrxR1) activity
GSH↓, Wang et al. demonstrated that PL could inhibit both glutathione and thioredoxin and thus induce ROS elevation,
Trx↓,
cMyc↓, downregulation of c-Myc and LMP1 and the Caspase-3-dependent apoptosis of Burkitt lymphoma cells in vitro.
Casp3↑,
Bcl-2↓, PL could downregulate Bcl-2 and Mcl-1 and decrease the expression of STAT-3
Mcl-1↓,
STAT3↓, Bharadwaj et al. identified PL as a direct STAT3 inhibitor
AR↓, Golovine et al. demonstrated for the first time that PL rapidly reduced the androgen receptor protein level of prostate cancer cells
DNAdam↑, inducing DNA damage,

2987- RES,    Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1
- in-vivo, Nor, NA
*VEGF↑, effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI.
*iNOS↑, Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1.
*NF-kB↑,
*Sp1/3/4↑,
*cardioP↑, demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI

3040- SK,    Pharmacological Properties of Shikonin – A Review of Literature since 2002
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA
*Half-Life↝, One study using H-shikonin in mice showed that shikonin was rapidly absorbed after oral and intramuscular administration, with a half-life in plasma of 8.79 h and a distribution volume of 8.91 L/kg.
*BioAv↓, shikonin is generally used in creams and ointments, that is, oil-based preparations; indeed, its insolubility in water is usually the cause of its low bioavailability
*BioAv↑, 200-fold increase in the solubility, photostability, and in vitro permeability of shikonin through the formation of a 1 : 1 inclusion complex with hydroxypropyl-β-cyclodextrin.
*BioAv↑, 181-fold increase in the solubility of shikonin in aqueous media in the presence of β-lactoglobulin at a concentra- tion of 3.1 mg/mL
*Inflam↓, anti-inflammatory effect of shikonin
*TNF-α↓, shikonin inhibited TNF-α production in LPS-stimulated rat primary macrophages as well as NF-κB translocation from the cytoplasm to the nucleus.
*other↑, authors found that treatment with shikonin prevented the shortening of the colorectum and decreased weight loss by 5 % while improving the ap- pearance of feces and preventing bloody stools.
*MPO↓, MPO activity was reduced as well as the expression of COX-2, the activation of NF-κB and that of STAT3.
*COX2↓,
*NF-kB↑,
*STAT3↑,
*antiOx↑, Antioxidant Effects of Shikonin
*ROS↓, radical scavenging activity of shikonin
*neuroP↑, shown to exhibit a neuroprotective effect against the damage caused by ischemia/reperfusion in adult male Kunming mice
*SOD↑, it also attenuated neuronal damage and the upregulation of superoxide dismutase, catalase, and glutathione peroxidase activities while reducing the glutathione/glutathione disulfide ratio.
*Catalase↑,
*GPx↑,
*Bcl-2↑, shikonin upregulated Bcl-2, downregulated Bax and prevented cell nuclei from undergoing morphological changes typical of apoptosis.
*BAX↓,
cardioP↑, Two different studies have suggested a possible cardioprotective effect of shikonin that would be related to its anti-inflammatory and antioxidant effects.
AntiCan↑, A wide spectrum of anticancer mechanisms of action have been described for shikonin:
NF-kB↓, suppression of NF-κB-regulated gene products [44],
ROS↑, ROS generation [46],
PKM2↓, inhibition of tumor-specific pyruvate kinase-M2 [47,48]
TumCCA↑, cell cycle arrest [49]
Necroptosis↑, or induction of necroptosis [50],
Apoptosis↑, shikonin at 1 μM induced caspase-dependent apoptosis in U937 cells after 6 h with an increase in DNA fragmentation, intracellular ROS, low mitochondrial membrane potential
DNAdam↑,
MMP↓,
Cyt‑c↑, At 10 μM, shikonin induced a greater release of cytochrome c from the mitochondria and of lactate dehydrogenase,
LDH↝,

2093- TQ,    Regulation of NF-κB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells
- in-vitro, Liver, HepG2 - in-vitro, Nor, NA
TumCD↑, evidence of the cytotoxic effects of TQ on HepG2 cells
selectivity↑, These findings indicate the selective regulation of HepG2 cell proliferation by TQ treatment without the detectable toxic effect of the normal hepatocytes
Casp3↑, TQ mediates the activation of Casp3, DLC1, and NF-κB, providing a new function of TQ in treating hepatocellular carcinoma (HCC).
DLC1↑,
NF-kB↑,
LDH↑, relative LDH production increased significantly in HepG2 cells treated with 500 ug/m
*toxicity↓, normal hepatocyte cells showed negligible differentiation in cell viability rate

3397- TQ,    Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
ChemoSen↑, TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development.
*Half-Life↝, These parameters remained associated with an elimination half-life (t1/2) of 63.43 ± 10.69 and 274.61 ± 8.48 min for intravenous and oral administration, respectively
*BioAv↝, TQ is characterized by slow absorption, rapid metabolism, rapid elimination and low physicochemical stability, which limits its pharmaceutical applications
*antiOx↑, Biologically active compounds from Nigella sativa have been shown to have antioxidant, antimicrobial, anti-inflammatory, antidiabetic, hepatoprotective, antiproliferative, proapoptotic, antiepileptic and immunomodulatory activities,
*Inflam↓,
*hepatoP↑,
TumCP↓, TQ exerts tumorigenic effects in a variety of ways, including modulation of the epigenetic machinery and effects on proliferation, the cell cycle, apoptosis, angiogenesis, carcinogenesis and metastasis
TumCCA↑,
Apoptosis↑,
angioG↑,
selectivity↑, TQ has low toxicity to normal cells, as confirmed by several studies, including studies on normal mouse kidney cells, normal human lung fibroblasts and normal human intestinal cells.
JNK↑, activation of c-Jun N-terminal kinases (JNK) and p38, as well as the phosphorylation of nuclear factor-?B (NF-?B) and the reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) activi
p38↑,
p‑NF-kB↑,
ERK↓,
PI3K↓,
PTEN↑, showing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3
Akt↓, TQ has also been shown to downregulate the PI3K/PTEN/Akt/mTOR and WNT/?-catenin pathways, which are critical for tumorigenesis
mTOR↓,
EMT↓, downregulating the epithelial to mesenchymal transition (EMT) transcription factors twist-related protein 1 (TWIST1) and E-cadherin
Twist↓,
E-cadherin↓,
ROS⇅, TQ has been shown to act as an antioxidant at low concentrations. Higher concentrations, however, induce apoptosis of cancer cells through the induction of oxidative stress
*Catalase↑, Thymoquinone upregulates the expression of genes encoding specific enzymes, such as catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase and glutathione peroxidase, whose role is to protect against reactive oxygen species
*SOD↑,
*GSTA1↑,
*GPx↑,
*PGE2↓, TQ has the ability to downregulate NF-?B, interleukin-1?, tumor necrosis factor alpha, cyclooxygenase-2 (COX-2,) matrix metalloproteinase 13 (MMP-13), prostaglandin E2 (PGE2), the interferon regulatory factor, which are associated with inflammation a
*IL1β↓,
*COX2↓,
*MMP13↓,
MMPs↓, Figure 2
TumMeta↓,
VEGF↓,
STAT3↓, TQ affects the induction of apoptosis in cancer cells by blocking the signal transducer and activator of transcription 3 (STAT3) signaling
BAX↑, upregulation of Bax and inhibition of Bcl-2 and B-cell lymphoma-extra large (Bcl-xl) expression, as well as activated caspase-9, -7 and -3, and induced cleavage of poly (ADP-ribose) polymerase (PARP).
Bcl-2↑,
Casp9↑,
Casp7↑,
Casp3↑,
cl‑PARP↑,
survivin↓, TQ also attenuated the expression of STAT3 target gene products, such as survivin, c-Myc and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21
cMyc↓,
cycD1/CCND1↓,
p27↑,
P21↑,
GSK‐3β↓, TQ reduces the levels of p-PI3K, p-Akt, p-glycogen synthase kinase 3 (p-GSK3?) and ?-catenin, thereby inhibiting downstream COX-2 expression, which in turn leads to a reduction in PGE2
β-catenin/ZEB1↓,
chemoP↑, results support the potential use of thymoquinone in colorectal cancer chemoprevention, as TQ is effective in protecting and treating the DMH-initiated early phase of colorectal cancer.

3113- VitC,    Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
- in-vitro, Nor, NA
TET2↑, intravenous vitamin C treatment in mice abrogates cancer progression through direct TET2 function restoration in cancer cells
NF-kB↑, Vitamin C triggers extensive demethylation at NF-κB/p65 binding sites

1832- VitK3,  VitC,    Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism
- in-vitro, AML, K562
ROS↑, vitamin K3- or vitamin C- induced apoptosis in leukemia cells by oxidative stress
H2O2↑, hydrogen peroxide generation,
NF-kB↑, activation of NF-κB,
P53↑, p53, c-Jun, protease caspase-3 activation
cJun↑,
Casp3↑,
MMP↓, mitochondria depolarization leading to nuclei fragmentation
DNAdam↑,
Dose?, Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM) or 100:1 (300 μM: 3 μM), respectively


Showing Research Papers: 1 to 40 of 40

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 40

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   Ferroptosis↑, 2,   GPx1↓, 1,   GPx4↑, 1,   GSH↓, 1,   H2O2↑, 3,   HO-1↓, 2,   Iron↑, 1,   Keap1↓, 1,   lipid-P↑, 1,   NRF2↓, 2,   NRF2↑, 1,   ROS↑, 18,   ROS⇅, 1,   mt-ROS↑, 1,   SOD↑, 2,   SOD2↓, 1,   Trx↓, 1,   TrxR1↓, 1,  

Metal & Cofactor Biology ⓘ

Tf↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 2,   CDC25↓, 1,   EGF↓, 1,   MEK↓, 2,   MMP↓, 11,   mtDam↑, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 1,   cMyc↓, 2,   p‑cMyc↑, 1,   Glycolysis↓, 2,   H2S↑, 1,   LDH↑, 1,   LDH↝, 1,   PI3K/Akt↑, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 6,   Apoptosis↑, 16,   BAD↑, 1,   BAX↑, 7,   Bax:Bcl2↑, 1,   Bcl-2↓, 8,   Bcl-2↑, 1,   cl‑BID↑, 1,   BIM↑, 1,   Casp↑, 3,   Casp3↑, 8,   cl‑Casp3↑, 3,   Casp7↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 3,   Casp9↑, 3,   cl‑Casp9↑, 1,   Cyt‑c↑, 9,   Diablo↑, 1,   DR5↑, 2,   Fas↑, 2,   Ferroptosis↑, 2,   hTERT/TERT↓, 2,   iNOS↓, 2,   iNOS↑, 2,   JNK↑, 3,   MAPK↓, 1,   MAPK↑, 2,   Mcl-1↓, 2,   MDM2↓, 1,   Necroptosis↑, 1,   NICD↓, 1,   p27↑, 2,   p38↑, 5,   survivin↓, 3,   Telomerase↓, 3,   TRAIL↑, 2,   TumCD↑, 2,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   cJun↑, 1,   ac‑H3↑, 1,   other↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   PERK↑, 1,  

Autophagy & Lysosomes ⓘ

LC3B-II↑, 1,   LC3II↑, 1,   p62↓, 1,   p‑p62↑, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

DNAdam↑, 9,   DNMT1↓, 1,   P53↑, 6,   p‑P53↑, 1,   cl‑PARP↑, 4,   PCNA↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 2,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 1,   P21↑, 5,   Securin↓, 1,   TumCCA?, 1,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

AR-V7?, 1,   cFos↓, 1,   EMT↓, 4,   ERK↓, 5,   p‑ERK↓, 1,   FOXM1↓, 1,   GSK‐3β↓, 2,   p‑GSK‐3β↓, 1,   HDAC↓, 1,   HDAC1↓, 1,   miR-125b↓, 1,   mTOR↓, 2,   NOTCH1↓, 1,   P90RSK↓, 1,   PI3K↓, 4,   PTEN↑, 1,   RAS↓, 1,   SCF↓, 1,   STAT3↓, 4,   STAT4↑, 1,   TAZ↓, 1,   TCF↑, 1,   TOP1↓, 3,   TumCG↓, 2,   Wnt↓, 2,  

Migration ⓘ

5LO↓, 1,   AEG1↓, 1,   AntiAg↑, 1,   Ca+2↑, 2,   DLC1↑, 1,   E-cadherin↓, 3,   E-cadherin↑, 1,   FAK↑, 1,   Fibronectin↓, 1,   MALAT1↓, 1,   MMP13↓, 1,   MMP2↓, 4,   MMP3↓, 1,   MMP9↓, 2,   MMPs↓, 2,   N-cadherin↓, 2,   NFAT↑, 1,   Snail↓, 1,   Snail↑, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 4,   TumCI↑, 1,   TumCMig↓, 3,   TumCP↓, 8,   TumCP↑, 2,   TumMeta↓, 2,   Twist↓, 1,   Twist↑, 1,   uPA↓, 1,   Vim↓, 1,   ZEB2↑, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   angioG↑, 1,   EGFR↓, 1,   HIF-1↓, 1,   Hif1a↓, 3,   NO↓, 1,   VEGF↓, 3,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CXCR4↓, 1,   DCells↑, 1,   IFN-γ↓, 1,   IFN-γ↑, 2,   IKKα↓, 1,   IKKα↑, 1,   IL12↑, 1,   IL15↑, 1,   IL1β↑, 1,   Inflam↓, 2,   NF-kB↓, 7,   NF-kB↑, 28,   p‑NF-kB↑, 3,   NK cell↑, 2,   p65↓, 1,   p‑p65↓, 1,   PGE2↓, 2,   TLR4↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   CDK6↓, 1,   CYP19?, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 10,   Dose?, 1,   Dose↑, 1,   Dose⇅, 1,   Dose∅, 1,   eff↓, 2,   eff↑, 8,   eff↝, 2,   MDR1↓, 1,   RadioS↑, 5,   selectivity↑, 10,   TET2↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 2,   EGFR↓, 1,   FOXM1↓, 1,   hTERT/TERT↓, 2,   LDH↑, 1,   LDH↝, 1,  

Functional Outcomes ⓘ

AntiCan↑, 5,   cardioP↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   chemoPv⇅, 1,   ChemoSideEff↓, 1,   neuroP↑, 2,   TumVol↓, 1,  
Total Targets: 230

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 3,   GPx↑, 2,   GSH↑, 2,   GSTA1↑, 1,   HO-1↑, 3,   lipid-P↓, 1,   MPO↓, 1,   NRF2↑, 4,   ROS↓, 4,   SOD↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   mitResp↑, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Cell Death ⓘ

Akt↑, 1,   BAX↓, 1,   Bcl-2↑, 1,   iNOS↑, 1,   MAPK↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↑, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

Choline↑, 1,   EMT↑, 1,   PI3K↑, 1,   STAT3↑, 1,  

Migration ⓘ

MMP13↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 2,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 4,   NF-kB↓, 1,   NF-kB↑, 9,   PGE2↓, 3,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 1,   BDNF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 5,   BioAv↝, 1,   Dose↝, 2,   eff↓, 1,   eff↑, 1,   Half-Life↓, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   IL6↓, 2,   NOS2↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   CardioT↓, 1,   chemoP↑, 1,   chemoPv↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 4,   toxicity↓, 5,  
Total Targets: 64

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
5 Betulinic acid
3 Silver-NanoParticles
2 Magnetic Fields
2 Ajoene (compound of Garlic)
2 Thymoquinone
2 Vitamin C (Ascorbic Acid)
1 Allicin (mainly Garlic)
1 Alpha-Lipoic-Acid
1 Radiotherapy/Radiation
1 alpha Linolenic acid
1 Artemisinin
1 beta-glucans
1 Baicalein
1 Berbamine
1 borneol
1 Boswellia (frankincense)
1 Carnosic acid
1 Celecoxib
1 chitosan
1 Chrysin
1 Docosahexaenoic Acid
1 eicosapentaenoic acid
1 Disulfiram
1 Copper and Cu NanoParticles
1 EGCG (Epigallocatechin Gallate)
1 Butyrate
1 Fisetin
1 Honokiol
1 Luteolin
1 Lycopene
1 Melatonin
1 Mushroom Chaga
1 Propolis -bee glue
1 Piperlongumine
1 Resveratrol
1 Shikonin
1 VitK3,menadione
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:214  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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