p65 Cancer Research Results

p65, RelA: Click to Expand ⟱

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P65, also known as RelA, is a subunit of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factor complex. NF-κB plays a crucial role in regulating immune response, inflammation, and cell survival.
Due to its role in cancer progression, p65 and the NF-κB pathway are considered potential therapeutic targets. Inhibitors of NF-κB signaling are being explored in preclinical and clinical studies as potential cancer treatments.
Many studies have reported that p65 is overexpressed in various types of cancers, including breast, prostate, lung, and colorectal cancers.
In some cancers, elevated p65 levels correlate with higher grades of tumors and advanced stages of disease.

"RELA proto-oncogene, NF-κB subunit." It encodes the p65 protein, which is a central component of the NF‑κB transcription factor complex.
-Chronic activation of RELA and the NF‑κB pathway is frequently associated with cancer progression, promoting inflammation-driven tumorigenesis, chemoresistance, and metastasis.
-RELA interacts with other oncogenic signaling networks (for example, STAT3 and MAPK pathways), further integrating environmental signals that favor cancer progression.

RELA (p65) is a critical subunit of the NF‑κB transcription factor complex, involved in the regulation of genes that control inflammation, cell survival, and proliferation. In the context of cancer, aberrant activation and overexpression of RELA are frequently associated with aggressive tumor behavior, therapy resistance, and poorer patient outcomes in cancers such as breast, lung, colorectal, and pancreatic cancers, among others.

RELA emerges as a potential key contributor to the suppression of glycolysis, mitochondrial respiration, and ATP production in cancer cells. (RELA knockdown signifcantly reduced the tumorigenic.
potential of various pancreatic cancer cell lines).

Scientific Papers found: Click to Expand⟱

1564-

Api,

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

in-vitro,

Pca,

22Rv1

10–80 μM

in-vivo,

NA,

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

2319-

Api,

Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis

in-vitro,

GBM,

 apigenin 20 mg/kg for 12 days

Glycolysis↓, Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues.
NF-kB↓,
p65↓,
Hif1a↓,
GLUT1↓,
GLUT3↓,
PKM2↓,
RadioS↑, Apigenin sensitizes the radiotherapy of SU3-5R cells-inoculated subcutaneous glioma
TumVol↓, Moreover, the tumor weight and relative tumor weight in the three treatment groups were significantly lower than those in the control group
TumW↓,

2606-

Ba,

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

Review,

HCC,

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

5556-

BBM,

Berbamine, a novel nuclear factor κB inhibitor, inhibits growth and induces apoptosis in human myeloma cells

in-vitro,

Melanoma,

TumCP↓, Berbamine inhibits the proliferation of KM3 cells in a dose- and time-dependent manner.
eff↑, Combination of berbamine with dexamethasone (Dex), doxorubicin (Dox) or arsenic trioxide (ATO) resulted in enhanced inhibition of cell growth.
TumCCA↑, KM3 cells were arrested at G1 phase and apoptotic cells increased from 0.54% to 51.83% for 36 h.
IKKα↓, Berbamine treatment led to increased expression of A20, down-regulation of IKKα, p-IκBα, and followed by inhibition of p65 nuclear localization.
p65↓,
Bcl-xL↓, As a result, NF-κB downstream targets such as cyclinD1, Bcl-xL, Bid and survivin were down-regulated.
BID↓,
survivin↓,

5551-

BBM,

Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis

vitro+vivo,

Bladder,

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

2745-

BetA,

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

in-vitro,

CRC,

RKO

in-vitro,

CRC,

SW480

in-vivo,

NA,

nude mice

Apoptosis↑, BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft
TumCG↓,
Sp1/3/4↓, BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells
survivin↓, decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1.
VEGF↓,
p65↓,
EGFR↓,
cycD1/CCND1↓,
ROS↑, due to induction of reactive oxygen species (ROS),
MMP↓, BA decreases MMP and induces ROS in RKO cells.

5875-

CA,

Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway

in-vivo,

IBD,

mice

*antiOx↑, Carnosic acid (CA) has been reported to possess antioxidative properties
*Weight↑, CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS).
*p65↓, CA decreased the activation of p65 and c-Jun signalling.
*cJun↓,
*NLRP3↓, CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity.
*Casp1↓,
*NRF2↑, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1,
*GSH↑, Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced.
*SOD↑,
*MDA↓,
*iNOS↓,
other↝, Moreover, many compounds from natural products, such as ellagic acid, gallic acid and quercetin, have been shown to prevent IBD through their antioxidative properties

5766-

CAPE,

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

in-vivo,

Nor,

rat

*MDA↓, CAPE-loaded-NL significantly counteracted ornithine-induced elevation in serum activities of pancreatic digestive enzymes and pancreatic levels of malondialdehyde, nuclear factor kappa B (NF-κB) p65, tumor necrosis factor-alpha, nitrite/nitrate, clea
*NF-kB↓,
*p65↓,
*TNF-α↓,
*cl‑Casp3↓,
*GSR↑, pretreatment with CAPE-loaded-NL significantly reinstated the ornithine-lowered glutathione reductase activity, glutathione,
*GSH↑,
*NRF2↑, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 levels and ATP/ADP ratio, and potentiated the Bcl-2/Bax ratio in pancreatic tissue.
*HO-1↑,
*Bax:Bcl2↓,
*antiOx↑, displayed superior antioxidant, anti-inflammatory and anti-apoptotic effects compared to free CAPE oral suspension
*Inflam↓,

1054-

CEL,

Celecoxib inhibited activation of NF-κB and expression of NF-κB P65 protein in HepG2 cells

in-vitro,

Liver,

HepG2

25 and 50 μmol/L

NF-kB↓,
p65↓,

5941-

Cela,

Celastrol inhibits migration and invasion through blocking the NF-κB pathway in ovarian cancer cells

in-vitro,

Ovarian,

SKOV3

in-vitro,

Ovarian,

OVCAR-3

TumCMig↓, At sub-toxic concentrations (<0.5 µM), celastrol inhibited migration and invasion in a concentration-dependent manner in SKOV-3 and OVCAR-3 cells.
TumCI↓,
NF-kB↓, celastrol blocked the canonical NF-κB pathway by inhibiting IκBα phosphorylation, and preventing IκBα degradation and p65 accumulation.
p65↓, blocking p65 translocation
MMP9↓, protein MMP-9, but not MMP-2, were inhibited by celastrol.
eff↑, Furthermore, celastrol showed no synergistic effect with MG132, an NF-κB inhibitor.
AntiTum↑, showing antitumor, anti-inflammatory, antihypertensive and antidiabetic activities
Inflam↓,
AntiDiabetic↑,

1577-

Citrate,

Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet

in-vivo,

PC,

30 mg·kg ·day citrate(injection)

mice

in-vitro,

PC,

PANC1

10 mmol·L citrate

in-vitro,

PC,

PATU-8988

in-vitro,

PC,

MIA PaCa-2

Apoptosis↑, citrate treatment demonstrates signifcant effcacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo
TumCP↓,
TumCG↑,
SPARC↑, citrate treatment reveal decreased glycolysis and oxygen consumption in tumor cells, increased SPARC protein expression, and the promotion of M1 polarization
Glycolysis↓,
OCR↓,
pol-M1↑, repolarizing M2 macrophages into M1 macrophages
pol-M2 MC↓, shift from the M2 phenotype to the M1 phenotype in TAMs following citrate treatment
Weight∅, no signficant changes in body weight observed between the two groups
ATP↓, decreased ATP production of pancreatic tumors in vivo
ECAR↓, signifcantly reduced glycolytic flux, glycolytic reserve, glycolytic capacity, and acidifcation rates
mitResp↓, decreased basal mitochondrial respiration
i-ATP↑, decrease in intracellular ATP levels
p65↓, citrate effectively suppressed the expression of RELA findings collectively underscore the critical role of RELA in mediating citrate's regulation of glycolysis and suppression of pancreatic cancer progression
i-Ca+2↑, inhibition of RELA resulted in a rapid elevation of intracellular calcium levels
eff↓, overexpression of RELA and SPARC knockdown attenuated the therapeutic effects of citrate

144-

CUR,

Bical,

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

in-vitro,

Pca,

PC3

 androgen-independent prostate cancer cells

in-vitro,

PC,

DU145

in-vitro,

PC,

LNCaP

p‑ERK↑, ERK1/2
p‑JNK↓, phosphorylation
MUC1↓, MUC1-C protein expression
p65↓,
AR↓, bicalutamide, an androgen receptor antagonist, inhibited cell growth in dose- and time-dependent fashion in PC3 and LNCaP cells.
TumCG↓,
MEK↑, curcumin inhibits the growth of androgen-independent prostate cancer cells through MEK/ERK1/2 and SAPK/JNK-mediated inhibition of p65, followed by reducing expression of MUC1-C protein.
SAPK↑, through activation of MEK/ERK/12 and SAPK/JNK

447-

CUR,

OXA,

Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway

vitro+vivo,

CRC,

HCT116

1, 2, 4, 8, 16, 32 and 64 μM, 48 h; 60 mg/kg, 3 weeks

4uM(Cur)+10uM(OXA)

p‑p65↓,
Bcl-2↓,
Casp3↑,
EMT↓,
p‑SMAD2↓,
p‑SMAD3↓,
N-cadherin↓,
TGF-β↓,
E-cadherin↑,
TumVol↓,
TumCMig↓,

2980-

CUR,

Inhibition of NF B and Pancreatic Cancer Cell and Tumor Growth by Curcumin Is Dependent on Specificity Protein Down-regulation

in-vivo,

PC,

mice

TumCG↓, curcumin inhibits Panc28 and L3.6pL pancreatic cancer cell and tumor growth in nude mice bearing L3.6pL cells as xenografts
p50↓, curcumin decreased expression of p50 and p65 proteins and NFkappaB-dependent transactivation and also decreased Sp1, Sp3, and Sp4 transcription factor
p65↓,
NF-kB↓,
Sp1/3/4↓,
MMP↓, Curcumin also decreased mitochondrial membrane potential and induced reactive oxygen species in pancreatic cancer cell
ROS↑,

2976-

CUR,

Curcumin suppresses the proliferation of oral squamous cell carcinoma through a specificity protein 1/nuclear factor‑κB‑dependent pathway

in-vitro,

Oral,

HSC3

in-vitro,

HNSCC,

CAL33

tumCV↓, Cur significantly inhibited the viability and colony formation ability of HSC3 and CAL33 cells.
Sp1/3/4↓, Cur decreased the expression of Sp1, p65 and HSF1 by suppressing their transcription levels.
p65↓,
HSF1↓,
NF-kB↓, Cur decreased NF‑κB activity in OSCC cells, and Sp1 downregulation enhanced the effect of Cur.

5006-

DSF,

Cu,

Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition

vitro+vivo,

lymphoma,

TumCD↑, n combination with a low concentration (1 μM) of Cu2+, DS induced cytotoxicity in Raji cells with an IC50 of 0.085 ± 0.015 μM and in Molt4 cells with an IC50 of 0.435 ± 0.109 μM.
TumCP↑, DS/Cu inhibits the proliferation of Raji cells in vivo.
Apoptosis↑, After exposure to DS (3.3 μM)/Cu (1 μM) for 24 hours, apoptosis was detected in 81.03 ± 7.91% of Raji cells
NRF2↓, After 24 h exposure, DS/Cu inhibits Nrf2 expression.
ROS↑, DS/Cu induced ROS generation.
p‑JNK↑, DS/Cu induced phosphorylation of JNK and inhibits p65 expression as well as Nrf2 expression both in vitro and in vivo.
p65↓,
eff↓, N-acetyl-L-cysteine (NAC), an antioxidant, can partially attenuate DS/Cu complex-induced apoptosis and block JNK activation in vitro.
NF-kB↓, Moreover, ROS-related activation of JNK pathway and inhibition of NF-κB and Nrf2 may also contribute to the DS/Cu induced apoptosis.

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

1005-

GI,

Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells

vitro+vivo,

Nor,

HUVECs

30uM

*NF-kB↓,
*p65↓, p65 was slightly decreased
*TLR4∅, protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired.
*angioG↓,
*TumCP↓,
*VEGF↓,
*Inflam↓,
*ICAM-1↓,
*VCAM-1↓,
*E-sel↓,
*p‑JNK↓,
*HO-1↑,

1087-

HNK,

Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE2-Mediated Activation of β-Catenin Signaling

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H460

in-vitro,

Lung,

H226

TumCMig↓,
COX2↓,
PGE2↓,
NF-kB↓,
p65↓,
β-catenin/ZEB1↓,
MMP2↓,
MMP9↓,

2864-

HNK,

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Review,

Var,

TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

2919-

LT,

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence

Review,

Var,

RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
ChemoSen↑,
chemoP↑,
*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
*Catalase↑,
*SOD↑,
*GPx↑,
*GSTs↑,
*GSH↑,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*IL10↑,
NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
HO-1↓,
NQO1↓,
GSH↓,
MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
p‑MET↓,
p‑Akt↓,
HGF/c-Met↓,
NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
Bcl-2↓,
SOD2↓,
Casp8↑,
Casp3↑,
PARP↑,
MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
NLRP3↓,
ASC↓,
Casp1↓,
IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
IKKα↓,
p‑p65↓,
p‑p38↑,
MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
ICAM-1↓,
EGFR↑,
p‑PI3K↓,
E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
ZO-1↑,
N-cadherin↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
Vim↑,
ITGB1↓,
FAK↓,
p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
Rac1↓,
Cdc42↓,
Rho↓,
PCNA↓, Lung cancer model ↓Cyclin B1, ↑p21, ↑p-Cdc2, ↓Vimentin, ↓MMP9, ↑E-cadherin, ↓AIM2, ↓Pro-caspase-1, ↓Caspase-1 p10, ↓Pro-IL-1β, ↓IL-1β, ↓PCNA
Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
AXL↓,
CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
NSE↓,
SOD↓,
Catalase↓,
GPx↓,
GSR↓,
GSTs↓,
GSH↓,
VitE↓,
VitC↓,
CYP1A1↓,
cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
AR↓, ↓Androgen receptor
AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
VEGF↓,
H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
H4↓,
HDAC↓,
SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
Cyt‑c↑,
p‑JNK↑,
PTEN↓, Lung cancer model 1/5/10/30/50/80/100 μmol/L ↑Cleaved caspase-3, ↑PARP, ↑Bax, ↓Bcl-2, ↓EGFR, ↓PI3K/Akt/PTEN/mTOR, ↓CD34, ↓PCNA
mTOR↓,
CD34↓,
FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
Fas↑,
XIAP↓,
p‑eIF2α↑,
CHOP↑,
LC3II↑,
PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
STAT3↓,
IL2↑,
EMT↓, Luteolin exerts anticancer activity by inhibiting EMT, and the possible mechanisms include the inhibition of the EGFR-PI3K-AKT and integrin β1-FAK/Src signaling pathways
cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
*Half-Life↝, ats administered an intraperitoneal injection of luteolin (60 mg/kg) absorbed it rapidly as well, with peak levels reached at 0.083 h (71.99 ± 11.04 μg/mL) and a prolonged half-life (3.2 ± 0.7 h)
*eff↑, Luteolin chitosan-encapsulated nano-emulsions increase trans-nasal mucosal permeation nearly 6-fold, drug half-life 10-fold, and biodistribution of luteolin in brain tissue 4.4-fold after nasal administration

3277-

Lyco,

Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent

Review,

Var,

antiOx↑, lycopene provides a strong antioxidant activity that is 100 times more effective than α-tocopherol and more than double effective that of β-carotene
TumCP↓, In vivo and in vitro experiments have demonstrated that lycopene at near physiological levels (0.5−2 μM) could inhibit cancer cell proliferation [[22], [23], [24]], induce apoptosis [[25], [26], [27]], and suppress metastasis [
Apoptosis↑,
TumMeta↑,
ChemoSen↑, lycopene can increase the effect of anti-cancer drugs (including adriamycin, cisplatin, docetaxel and paclitaxel) on cancer cell growth and reduce tumour size
BioAv↓, low water solubility and bioavailability of lycopene
Dose↝, The concentration of lycopene in plasma (daily intake of 10 mg lycopene) is approximately 0.52−0.6 μM
BioAv↓, significant decrease in lycopene bioavailability in the elderly
BioAv↑, oils and fats favours the bioavailability of lycopene [80], while large molecules such as pectin can hinder the absorption of lycopene in the small intestine due to their action on lipids and bile salt molecules
SOD↑, GC: 50−150 mg/kg BW/day ↑SOD, CAT, GPx ↑IL-2, IL-4, IL-10, TNF-α ↑IgA, IgG, IgM ↓IL-6
Catalase↑,
GPx↑,
IL2↑, lycopene treatment significantly enhanced blood IL-2, IL-4, IL-10, TNF-α levels and reduced IL-6 level in a dose-dependent manner.
IL4↑,
IL1↑,
TNF-α↑,
GSH↑, GC: ↑GSH, GPx, GST, GR
GPx↑,
GSTA1↑,
GSR↑,
PPARγ↑, ↑GPx, SOD, MDA ↑PPARγ, caspase-3 ↓NF-κB, COX-2
Casp3↑,
NF-kB↓,
COX2↓,
Bcl-2↑, AGS cells Lycopene 5 μM ↑Bcl-2 ↓Bax, Bax/Bcl-2, p53 ↓Chk1, Chk2, γ-H2AX, DNA damage ↓ROS Phase arrest
BAX↓,
P53↓,
CHK1↓,
Chk2↓,
γH2AX↓,
DNAdam↓,
ROS↓,
P21↑, CRC: ↑p21 ↓PCNA, β-catenin ↓COX-2, PGE2, ERK1/2 phosphorylated
PCNA↓,
β-catenin/ZEB1↓,
PGE2↓,
ERK↓,
cMyc↓, AGS cells: ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS
cycE/CCNE↓,
JAK1↓,
STAT3↓,
SIRT1↑, Huh7: ↑SIRT1 ↓Cells growth ↑PARP cleavage ↓Cyclin D1, TNFα, IL-6, NF-κB, p65, STAT3, Akt activation ↓Tumour multiplicity, volume
cl‑PARP↑,
cycD1/CCND1↓,
TNF-α↓,
IL6↓,
p65↓,
MMP2↓, SK-Hep1 human hepatoma cells Lycopene 5, 10 μM ↓MMP-2, MMP-9 ↓
MMP9↓,
Wnt↓, AGS cells Lycopene 0.5 μM, 1 μM ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS

204-

MFrot,

MF,

Rotating magnetic field improved cognitive and memory impairments in a sporadic ad model of mice by regulating microglial polarization

in-vivo,

AD,

 0.2T, 4Hz

 reduced aluminum deposition in the brains of AD mice

*NF-kB↓, RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway.
*MAPK↓,
*TLR4↓,
*memory↑,
*cognitive↑,
*TGF-β1↑, RMF treatment promoted the expression of anti-inflammatory cytokines (TGF-β1, Arg-1, IL-4, IL-10)
*ARG↑, Arg-1
*IL4↑,
*IL10↑,
*IL6↓,
*IL1↓, IL-1β
*TNF-α↓,
*iNOS↓,
*ROS↓, in mice brain
*NO↓, in serum
*MyD88↓,
*p‑IKKα↓, phosphorylated IKKα/β, IкBα, NF-кB p65, JNK, p38,
*p‑IκB↓, IкBα
*p‑p65↓,
*p‑JNK↓,
*p‑p38↓,
*ERK↓,
*neuroP↑, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice.
*Aβ↓, RMF treatment reduced Aβ deposition in the AD model mice

4643-

OLE,

HT,

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Review,

Var,

TumCCA↑, A similar S phase cell cycle arrest was also observed for 800 μM HT, and induction of apoptosis also took place after 24 h incubation of HT-29 cells with 600 μM and 800 μM HT
Apoptosis↑,
ER Stress↑, 400 μM HT triggered endoplasmic reticulum stress in HT-29 cells, with activation of unfolded protein response,
UPR↑,
CHOP↑, increase in CHOP protein levels (responsible for ROS production and Bcl-2 downregulation) and NADPH oxidase 4 (NOX4)
ROS↑,
Bcl-2↓,
NOX4↑,
Hif1a↓, Moreover, 400 μM HT reduced HIF-1α protein levels
MMP2↓, figure 2
MMP↓,
VEGF↓,
Akt↓,
NF-kB↓,
p65↓,
SIRT3↓,
mTOR↓,
Catalase↓,
SOD2↓,
FASN↓,
STAT3↓,
HDAC2↓,
HDAC3↓,
BAD↑, figure 2 upregulated
BAX↑,
Bak↑,
Casp3↑,
Casp9↑,
PARP↑,
P53↑,
P21↑,
p27↑,
Half-Life↝, HT added to extra virgin olive oil produced a plasma peak of 3.79 ng/mL after 30 min, followed by a rapid decline in HT plasma concentration
BioAv↓, On the basis of these pieces of data, it becomes evident that cytotoxicity and anti-cancer effects of OLE and HT were recorded at concentrations largely exceeding those reachable with diet/olive oil consumption
BioAv↓, Thus, it is difficult to imagine how OLE and HT may be used as cancer-preventive/treating agents if the route of administration is ingestion.
selectivity↑, However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells,
RadioS↑, 200 μM OLE enhanced cell radiosensitivity in vitro and in vivo after injection in BALB/C nude mice
*ROS↓, A lot of experimental data in vivo and in vitro have definitively demonstrated the ROS scavenger ability of OLE and HT, which can also act on antioxidant cellular mechanisms restoring ROS homeostasis,
*GSH↑, including promotion of the increase in reduced glutathione levels (GSH), depletion of lipid peroxidation product malondialdehyde (MDA), intensification of the expression and/or activity of detoxicating enzymes SOD, CAT, glutathione-S-transferase (GST
*MDA↓,
*SOD↑,
*Catalase↑,
*NRF2↑, and nuclear factor E2-related factor 2 (Nrf2) upregulation/transactivation,
*chemoP↑, OLE and HT have shown an important ability to mitigate the toxicity elicited by chemotherapeutic agents mainly through their largely demonstrated antioxidant and ROS scavenger activity.
*Inflam↓, OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models,
PPARγ↑, HT-dependent anti-inflammatory effect was also mediated by HT-elicited increase in protein levels of PPARγ

1672-

PBG,

The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers

Review,

BC,

ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

3251-

PBG,

The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways

Review,

AD,

Review,

Diabetic,

Review,

Var,

in-vitro,

Nor,

H9c2

To induce oxidative stress, H9c2 cells were exposed to multiple H2O2 concentrations (0, 50, 100, 150, 200, and 250 μM) for 1 h

*antiOx↑, In this study, the antioxidant and anti-inflammatory effects of the main flavonoids of propolis (chrysin, pinocembrin, galangin, and pinobanksin) and propolis extract were researched.
*Inflam↓,
*ROS↓, ROS levels were decreased; SOD and CAT activities were increased; and the expression of HO-1 protein was increased by chrysin.
*SOD↑,
*Catalase↑,
*HO-1↑,
*NO↓, The results demonstrated that NO (Nitric Oxide), NOS (Nitric Oxide Synthase), and the activation of the NF-κB signaling pathway were inhibited in a dose-dependent manner
*NOS2↓,
*NF-kB↓,
*NRF2↑, it is possible that phytochemicals activate the Nrf2 pathway and inhibited the NF-κB (Nuclear factor kappa B) pathway.
*hepatoP↑, propolis has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, and hepatoprotective properties.
*MDA↓, chrysin reduced the cytotoxicity, MDA levels, and lysosomal and mitochondrial damage induced by AlP in a dose-dependent manner and increased the GSH activity induced by AlP i
*mtDam↓,
*GSH↑,
*p65↓, Similarly, galangin at 15, 30, and 60 mg/kg inhibited the expression of NF-κB p65, NOS, TNF-α, and IL-1β in a dose-dependent manner
*TNF-α↓,
*IL1β↓,
*NRF2↑, Nrf2 translocation from the cytoplasm to the nucleus was up-regulated (chrysin range of 5 μM–10 μM, pinocembrin range of 5 μM–40 μM, and propolis-extract range of 5 μg/mL–40 μg/mL)
*NRF2↓, and then down-regulated (chrysin range of 15 μM–25 μM, pinocembrin range of 40 μM–60 μM, and propolis-extract range of 40 μg/mL–100 μg/mL) following treatments with chrysin, pinocembrin, and propolis extract
*ROS⇅, Secondly, chrysin, pinocembrin, galangin, pinobanksin, and propolis extract exhibited antioxidant and pro-oxidant effects in a dose-dependent manner.
*BioAv↓, bioavailability values of galangin and chrysin in propolis extracts were determined in a study, and they were at 7.8% and 7.5%, respectively
*BioAv↑, Moreover, propolis extract has a higher bioavailability than single-flavonoid standards

5185-

PEITC,

SFN,

Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells

in-vitro,

Pca,

PC3

NF-kB↓, treatment with SFN (20 and 30 microM) and PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells.
p65↓,
VEGF↓,
cycD1/CCND1↓,
Bcl-xL↓,
IKKα↓, mainly mediated through the inhibition of IKK phosphorylation, particularly IKKbeta

5210-

PI,

Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells

in-vitro,

Melanoma,

B16-BL6

2.5, 5 and 10 microg/ml

IL1β↓, IL-1beta, IL-6, TNF-alpha and GM-CSF. Piperine treatment significantly reduced the above proinflammatory cytokines.
TNF-α↓,
MMPs↓, Piperine could inhibit the matrix metalloproteinase production
p65↓, p65, p50, c-Rel subunits of NF-kappaB and other transcription factors such as ATF-2, c-Fos and CREB were inhibited by the treatment of piperine.
p50↓,
NF-kB↓,
ATF2↓,
cFos↓,
CREB↓,

3597-

PI,

Chronic diseases, inflammation, and spices: how are they linked?

Review,

AD,

Review,

Park,

Review,

Var,

*NF-kB↓, downregulation of inflammatory pathways such as NF-κB, MAPK, AP-1, COX-2, NOS-2, IL-1β, TNF-α, PGE2, STAT3
*MAPK↓,
*AP-1↓,
*COX2↓,
*NOS2↓,
*IL1β↓, Parkinson’s disease ↓IL-1β, ↓TNF-α
*TNF-α↓,
*PGE2↓,
*STAT3↓,
*IL10↑, Arthritis ↑IL-10
*IL4↓, Asthma ↓IL-4, -5, ↓NF-κB
*IL5↓,
P53↑, Breast cancer ↑p53, ↓MMP-9,-2, ↓c-Myc, ↓VEGF
MMP9↓,
MMP2↓,
cMyc↓,
VEGF↓,
STAT3↓, Gastric cancer ↓STAT3
survivin↓, Triple negative breast cancer ↓Survivin, ↓p65
p65↓,

3534-

QC,

Lyco,

Synergistic protection of quercetin and lycopene against oxidative stress via SIRT1-Nox4-ROS axis in HUVEC cells

in-vitro,

Nor,

HUVECs

*ROS↓, especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production.
*NOX4↓, Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress
*Inflam↓, quercetin-lycopene combination downregulated inflammatory genes induced by H2O2, such as IL-17 and NF-κB.
*NF-kB↓, NF-κB p65 was activated by H2O2 but inhibited by the quercetin-lycopene combination.
*p65↓,
*SIRT1↑, quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity
*cardioP↑, The cardioprotective role of SIRT1
*IL6↓, LYP: Q = 1:5), interacted with deacetylase SIRT1 to inhibit NF-κB p65 and Nox4 enzyme, downregulated inflammatory cytokines such as IL-6 and pro-inflammatory enzymes such as COX-2, and suppressed ROS elevation activated by H2O2.
*COX2↓,

3372-

QC,

FIS,

KaempF,

Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers

Review,

HNSCC,

ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
TumCCA↓, inhibition of the cell cycle;
HSPs↓, inhibition of heat shock proteins;
RAS↓, inhibition of Ras protein expression.
ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
Ca+2↑,
MMP↓,
Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
Endon↑,
MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
MMP2↓,
MMP7↓,
MMP-10↓,
VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
NF-kB↓,
p65↓,
iNOS↓,
COX2↓,
uPA↓,
PI3K↓,
FAK↓,
MEK↓,
ERK↓,
JNK↓,
p38↓,
cJun↓,
FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a

2566-

RES,

A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke

Review,

Stroke,

*neuroP↑, comprehensive overview of resveratrol's neuroprotective role in IS
*NRF2↑, Findings from previous studies suggest that Nrf2 activation can significantly reduce brain injury following IS and lead to better outcomes
*SIRT1↑, neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways.
*PGC-1α↑, IRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO)
*FOXO↑,
*HO-1↑, ctivation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic bra
*NQO1↑,
*ROS↓,
*BP↓, Multiple studies have demonstrated that resveratrol presented protective effects in IS, it can mediate blood pressure and lipid profiles which are the main key factors in managing and preventing stroke
*BioAv↓, The residual quantity of resveratrol undergoes metabolism, with the maximum reported concentration of free resveratrol being 1.7–1.9 %
*Half-Life↝, The levels of resveratrol peak 60 min following ingestion. Another study found that within 6 h, there was a further rise in resveratrol levels. This increase can be attributed to intestinal recirculation of metabolites
*AMPK↑, Resveratrol also increases AMPK and inhibits GSK-3β (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces ROS
*GSK‐3β↓,
*eff↑, Furthermore, oligodendrocyte survival is boosted by resveratrol, which may help to preserve brain homeostasis following a stroke
*AntiAg↑, resveratrol may suppress platelet activation and aggregation caused by collagen, adenosine diphosphate, and thrombin
*BBB↓, Although resveratrol is a highly hydrophobic molecule, it is exceedingly difficult to penetrate a membrane like the BBB. However, an alternate administration is through the nasal cavity in the olfactory area, which results in a more pleasant route
*Inflam↓, Resveratrol's anti-inflammatory effects have been demonstrated in many studies
*MPO↓, Resveratrol dramatically lowered the amounts of cerebral infarcts, neuronal damage, MPO activity, and evans blue (EB) content in addition to neurological impairment scores.
*TLR4↓, TLR4, NF-κB p65, COX-2, MMP-9, TNF-α, and IL-1β all had greater levels of expression after cerebral ischemia, whereas resveratrol decreased these amounts
*NF-kB↓,
*p65↓,
*MMP9↓,
*TNF-α↓,
*IL1β↓,
*PPARγ↑, Previous studies have shown that resveratrol activates the PPAR -γ coactivator 1α (PGC-1 α), which has free radical scavenging properties
*MMP↑, Resveratrol can prevent mitochondrial membrane depolarization, preserve adenosine triphosphate (ATP) production, and inhibit the release of cytochrome c
*ATP↑,
*Cyt‑c∅,
*mt-lipid-P↓, mitochondrial lipid peroxidation (LPO), protein carbonyl, and intracellular hydrogen peroxide (H2O2) content were significantly reduced in the resveratrol treatment group, while the expression of HSP70 and metallothionein were restored
*H2O2↓,
*HSP70/HSPA5↝,
*Mets↝,
*eff↑, Shin et al. showed that 5 mg/kg intravenous (IV) resveratrol reduced infarction volume by 36 % in an MCAO mouse model.
*eff↑, This study indicates that resveratrol holds the potential to improve stroke outcomes before ischemia as a pre-treatment strategy
*motorD↑, resveratrol treatment significantly reduced infarct volume and prevented motor impairment, increased glutathione, and decreased MDA levels compared to the control group,
*MDA↓,
*NADH:NAD↑, Resveratrol treatment significantly enhanced the intracellular NAD+/NADH ratio
eff↑, Pretreatment with resveratrol (20 or 40 mg/kg) significantly lowered the cerebral edema, infarct volume, lipid peroxidation products, and inflammatory markers
eff↑, Intraperitoneal administration of resveratrol at a dose of 50 mg/kg reduced cerebral ischemia reperfusion damage, brain edema, and BBB malfunction

3068-

RES,

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

in-vitro,

lymphoma,

U937

p65↓, In our study, RESV treatment significantly decreased p65 expression and reduced the activities of the antioxidant enzymes SOD2, PRX2, CAT, and TRX.
SOD2↓,
Prx↓,
Catalase↓,
Trx↓,
TNF-α↓, (i.e., TNF-α, IL-8, and MCP-1), whereas a reduction in the protein levels of these cytokines was observed in the presence of RESV.
IL8↓,
MCP1↓,
SIRT1↑, a trend of increased SIRT1 activity in the presence of RESV was observed, which may be due to the low dose of RESV used

1746-

RosA,

Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells

in-vitro,

AML,

U937

TNF-α↓, Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-α-induced NF-κB activation in human dermal fibroblasts.
ROS↓, RA treatment significantly sensitizes TNF-α-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-κB) and reactive oxygen species (ROS).
Casp↑, Activation of caspases in response to TNF-α was markedly increased by RA treatment
NF-kB↓, RA also suppressed NF-κB activation through inhibition of phosphorylation and degradation of IκBα, and nuclear translocation of p50 and p65
IκB↓,
p50↓,
p65↓,
IAP1↓, This inhibition was correlated with suppression of NF-κB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP)
IAP2↓,
XIAP↓,
Apoptosis↑, These results demonstrated that RA inhibits TNF-α-induced ROS generation and NF-κB activation, and enhances TNF-α-induced apoptosis.

1745-

RosA,

Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications

Review,

Var,

Review,

AD,

ChemoSideEff↓, updated review is to highlight the chemopreventive and chemotherapeutic effects of RA and its derivatives
ChemoSen↑,
antiOx↑, RA also showed antioxidant effects and suppressed the activity and expression of matrix metalloproteinase (MMP)− 2,9
MMP2↓,
MMP9↓,
p‑AMPK↑, show that RA prevents metastasis through AMPK phosphorylation and suppresses CRC cell growth
DNMTs↓, RA allegedly suppressed DNA methyltransferase activity in the human breast cancer MCF7 cell line
tumCV↓, A549 lung cancer cells were 50% suppressed by RA, which also prevented COX-2 activity in these cells.
COX2↓,
E-cadherin↑, upregulating E-cadherin expression while downregulating Vimentin and N-cadherin expression, indicating that RA could inhibit hepatocellular carcinoma cells' ability to invade by MMPs and EMT
Vim↓,
N-cadherin↓,
EMT↓,
Casp3↑, The activation of caspase-3 and caspase-9 by RA also prevented the migration and invasion of liver cancer cells
Casp9↓,
ROS↓, In addition to reducing ROS, RA also enhanced GSH synthesis, lowered the expression of MMP-2 and MMP-9
GSH↑,
ERK↓, By inhibiting ERK and Akt activation, RA may stop the progression of colon cancer
Akt↓,
ROS↓, In U937 cells, it has been demonstrated that treatment with RA in concentrations 60 µM suppresses ROS and NF-kB by blocking IκB-α from being phosphorylated and degraded and the nuclear translocation of p50 and p65
NF-kB↓,
p‑IκB↓,
p50↓,
p65↓,
neuroP↑, RA can prevent the pathophysiology of Alzheimer's disease by reducing Aβ aggregation
Dose↝, 60 µM suppresses ROS and NF-kB by blocking IκB-α from being phosphorylated and degraded and the nuclear translocation of p50 and p65

3003-

RosA,

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases

Review,

Var,

Review,

AD,

Review,

Park,

*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

4441-

SeNPs,

The Role of Selenium Nanoparticles in the Treatment of Liver Pathologies of Various Natures

Review,

Nor,

*ROS↓, liver is the depot for most selenoproteins, which can reduce oxidative stress, inhibit tumor growth, and prevent other liver damage.
*hepatoP↑, their hepatoprotective properties
*selenoP↑,
*ALAT↓, (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP). However, the introduction of SeNPs significantly reduced the change in the level of these enzymes
*AST↓,
*GSH↑, significant increase in the content of glutathione and glutathione peroxidase in the liver
*GPx↑,
*TNF-α↓, In addition, the expression level of TNF-α, IL-6, NF-kB, and p65 genes was significantly increased in the cadmium-treated group (compared with the control), co-treatment of SeNPs and lacto-SeNPs led to a decrease in the expression of these genes.
*IL6↓,
*NF-kB↓,
*p65↓,
*Dose⇅, lactobacilli were used to restore Se from sodium selenite, while the synthesized nanoparticles had a size of 42.4 ± 10.5 nm and a zeta potential of −36.6 mV.

2211-

SK,

Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways

in-vivo,

ostP,

mice, RANKL-induced

*BMD↑, Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo.
*p‑NF-kB↓, shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38.
*p‑p50↓, by inhibiting phosphorylation of P65, P50, and IkB protein.
*p‑p65↓,
*p‑ERK↓, shikonin blocked the MAPK pathway via preventing phosphorylation of ERK, JNK, and P38
*p‑cJun↓,
*p‑p38↓,

2210-

SK,

Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway

in-vitro,

BC,

MGC803

1.854 μm

TumCA↓, Shikonin (1 μm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells.
TumCI↓,
TumCMig↓,
MMP2↓, matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB
MMP7↓,
TLR2↓,
p65↓,
NF-kB↓,
eff↑, In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone.
ROS↑, Shikonin-induced ROS generation

5111-

SSE,

Sodium selenite induces apoptosis via ROS-mediated NF-κB signaling and activation of the Bax-caspase-9-caspase-3 axis in 4T1 cells

in-vitro,

BC,

4T1

ROS↑, SSE treatment causes a transient increase in intracellular reactive oxygen species (ROS) levels, resulting in the inhibition of nuclear transcription factor-κB (NF-κB) signaling and p65
NF-kB↓,
p65↓,
mtDam↑, the accumulation of ROS caused mitochondrial dysfunction, leading to the activation of caspase-9 and -3, thereby resulting in apoptosis.
Casp9↑,
Casp3↑,
Apoptosis↑,
eff↓, However, modulation of the ROS level by the chemical inhibitor N-acetyl-cysteine (NAC)reversed these events.

5112-

SSE,

https://pubmed.ncbi.nlm.nih.gov/19811770/

in-vitro,

Pca,

PC3

VEGF↓, pretreatment with selenium (0.5-5uM) inhibited the LPS-induced expression of TGFbeta(1) and VEGF and production of these cytokines and IL-6 by PC3 cells,
IL6↓,
NF-kB↓, 3 and 5uM significantly inhibited the translocation of the NF-(K)B p65 subunit to the nucleus in LPS-stimulated PC3 cells.
p65↓,

5222-

TQ,

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

in-vitro,

CRC,

COLO205

40 µM TQ

in-vitro,

CRC,

HCT116

tumCV↓, TQ significantly decreased cell viability in COLO205 and HCT116 cells in a dose-dependent manner.
ChemoSen↑, TQ treatment additionally sensitized COLO205 and HCT116 cells to cisplatin therapy in a concentration-dependent manner.
p‑p65↓, TQ treatment significantly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TQ treatment.
NF-kB↓,
VEGF↓, TQ also decreased the expression levels of VEGF, c-Myc and Bcl-2.
cMyc↓,
Bcl-2↓,
ROS↑, TQ-induced apoptosis has been indicated to be mediated by reactive oxygen species generation (29,33,37)

2127-

TQ,

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

Review,

GBM,

chemoP↑, TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells
ChemoSen↑,
BioAv↑, TQ adds another advantage in overcoming blood-brain barrier
PTEN↑, TQ upregulates PTEN signaling [72, 73], interferes with PI3K/Akt signaling and promotes G(1) arrest, downregulates PI3K/Akt
PI3K↓,
Akt↓,
TumCCA↓,
NF-kB↓, and NF-κB and their regulated gene products, such as p-AKT, p65, XIAP, Bcl-2, COX-2, and VEGF, and attenuates mTOR activity
p‑Akt↓,
p65↓,
XIAP↓,
Bcl-2↓,
COX2↓,
VEGF↓,
mTOR↓,
RAS↓, Studies in colorectal cancer have demonstrated that TQ inhibits the Ras/Raf/MEK/ERK signaling
Raf↓,
MEK↓,
ERK↓,
MMP2↓, Multiple studies have reported that TQ downregulates FAC and reduces the secretion of MMP-2 and MMP-9 and thereby reduces GBM cells migration, adhesion, and invasion
MMP9↓,
TumCMig↓,
TumCI↓,
Casp↑, caspase activation and PARP cleavage
cl‑PARP↑,
ROS⇅, TQ is hypothesized to act as an antoxidant at lower concentrations and a prooxidant at higher concentrations depending on its environment [89]
ROS↑, In tumor cells specifically, TQ generates ROS production that leads to reduced expression of prosurvival genes, loss of mitochondrial potential,
MMP↓,
eff↑, elevated level of ROS generation and simultaneous DNA damage when treated with a combination of TQ and artemisinin
Telomerase↓, inhibition of telomerase by TQ through the formation of G-quadruplex DNA stabilizer, subsequently leads to rapid DNA damage which can eventually induce apoptosis in cancer cells specifically
DNAdam↑,
Apoptosis↑,
STAT3↓, TQ has shown to suppress STAT3 in myeloma, gastric, and colon cancer [86, 171, 172]
RadioS↑, TQ might enhance radiation therapeutic benefit by enhancing the cytotoxic efficacy of radiation through modulation of cell cycle and apoptosis [31]

2084-

TQ,

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

Review,

Var,

*ROS↓, An interesting study reported that thymoquinone is actually a potent apoptosis inducer in cancer cells, but it exerts antiapoptotic effect through attenuating oxidative stress in other types of cell injury
*chemoPv↑, antioxidant activity of thymoquinone is responsible for its chemopreventive activities
ROS↑, other studies reported thymoquinone induce apoptosis in cancer cells by exerting oxidative damage
ROS⇅, Another hypothesis states that thymoquinone acts as an antioxidant at lower concentrations and a prooxidant at higher concentrations
MUC4↓, Torres et al. [17] revealed that thymoquinone down-regulates glycoprotein mucin 4 (MUC4)
selectivity↑, thymoquinone was found to inhibit DNA synthesis, proliferation, and viability of cancerous cells, such as LNCaP, C4-B, DU145, and PC-3, but not noncancerous BPH-1 prostate epithelial cells [20].
AR↓, Down-regulation of androgen receptor (AR) and cell proliferation regulator E2F-1 was indicated as the mechanism behind thymoquinone’s action in prostate cancer
cycD1/CCND1↓, expression of STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1 and vascular endothelial growth factor (VEGF), was inhibited by thymoquinone, which ultimately increased apoptosis and killed cancer cells
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Mcl-1↓,
VEGF↓,
cl‑PARP↑, induction of the cleavage of poly-(ADP-ribose) polymerase (PARP
ROS↑, In ALL cell line CEM-ss, thymoquinone treatment generated reactive oxygen species (ROS) and HSP70
HSP70/HSPA5↑,
P53↑, thymoquinone can induce apoptosis in MCF-7 breast cancer cells via the up-regulation of p53 expression
miR-34a↑, Thymoquinone significantly increased the expression of miR-34a via p53, and down-regulated Rac1 expression
Rac1↓,
TumCCA↑, In hepatic carcinoma, thymoquinone induced cell cycle arrest and apoptosis by repressing the Notch signaling pathway
NOTCH↓,
NF-kB↓, Evidence revealed that thymoquinone suppresses tumor necrosis factor (TNF-α)-induced NF-kappa B (NF-κB) activation
IκB↓, consequently inhibits the activation of I kappa B alpha (I-κBα) kinase, I-κBα phosphorylation, I-κBα degradation, p65 phosphorylation
p‑p65↓,
IAP1↓, down-regulated the expression of NF-κB -regulated antiapoptotic gene products, like IAP1, IAP2, XIAP Bcl-2, Bcl-xL;
IAP2↑,
XIAP↓,
TNF-α↓, It also inhibited monocyte chemo-attractant protein-1 (MCP-1), TNF-α, interleukin (IL)-1β and COX-2, ultimately reducing the NF-κB activation in pancreatic ductal adenocarcinoma cells
COX2↓,
Inflam↓, indicating its role as an inhibitor of proinflammatory pathways
α-tubulin↓, Without affecting the tubulin levels in normal human fibroblast, thymoquinone induces degradation of α and β tubulin proteins in human astrocytoma U87 cells and in T lymphoblastic leukaemia Jurkat cells, and thus exerts anticancer activity
Twist↓, thymoquinone treatment inhibits TWIST1 promoter activity and decreases its expression in breast cancer cell lines; leading to the inhibition of epithelial-mesenchymal transition (EMT)
EMT↓,
mTOR↓, thymoquinone also attenuated mTOR activity, and inhibited PI3K/Akt signaling in bladder cancer
PI3K↓,
Akt↓,
BioAv↓, Thymoquinone is chemically hydrophobic, which causes its poor solubility, and thus bioavailability. bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min
ChemoSen↑, Some studies revealed that thymoquinone in combination with other chemotherapeutic drugs can show better anticancer activities
BioAv↑, Thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100 nm were found to maintain stability, improve bioavailability and maintain thymoquinone’s anticancer activity
PTEN↑, Thymoquinone also induces apoptosis by up-regulating PTEN
chemoPv↑, A recent study showed that thymoquinone can potentiate the chemopreventive effect of vitamin D during the initiation phase of colon cancer in rat model
RadioS↑, thymoquinone also mediates radiosensitization and cancer chemo-radiotherapy
*Half-Life↝, Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) has been developed to improve its bioavailability (elimination half-life ~5 hours)
*BioAv↝, calculated absolute bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min by Alkharfy et al.

3427-

TQ,

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

3573-

TQ,

Chronic diseases, inflammation, and spices: how are they linked?

Review,

Var,

NF-kB↓, Bladder cancer ↓NF-κB, ↓XIAP
XIAP↓,
PI3K↓, Cholangiocarcinoma ↓PI3K/Akt, ↓NF-κB
Akt↓,
STAT3↓, Gastric cancer ↓STAT3, ↓JAK2, ↓c-Src
JAK2↓,
cSrc↓,
PCNA↓, Lung cancer ↓PCNA, ↓CD1, ↓MMP-2, ↓ERK1/2
MMP2↓,
ERK↓,
Ki-67↓, Multiple myeloma ↓Ki-67, ↓VEGF, ↓Bcl-2, ↓p65
Bcl-2↓,
VEGF↓,
p65↓,
COX2↓, Myeloid leukemia ↓NF-κB, ↓CD1, ↓COX-2, ↓MMP-9
MMP9↓,

1821-

VitK3,

Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration

in-vitro,

Oral,

in-vitro,

Nor,

HEK293

in-vitro,

Nor,

HaCaT

selectivity↑, menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells.
TumCD↓,
BAX↑, increased the expression of pro-apoptotic proteins, Bax and p53
P53↑,
Bcl-2↓, concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65
p65↓,
E-cadherin↑, Menadione induced the expression of E-cadherin
EMT↓, but reduced the expression of EMT markers, vimentin and fibronectin
Vim↓,
Fibronectin↓,
TumCG↓, Menadione also inhibited anchorage independent growth and migration in SAS cells.
TumCMig↓,

Showing Research Papers: 1 to 47 of 47

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 47

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 6, Catalase↑, 3, GPx↑, 2, GSH↑, 6, GSR↑, 1, GSTs↑, 1, H2O2↓, 1, HO-1↑, 4, lipid-P↓, 1, mt-lipid-P↓, 1, MDA↓, 5, Mets↝, 1, MPO↓, 1, NOX4↓, 1, NQO1↑, 1, NRF2↓, 1, NRF2↑, 7, ROS↓, 9, ROS⇅, 1, selenoP↑, 1, SOD↑, 4,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1, MMP↑, 2, mtDam↓, 1, PGC-1α↑, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, AMPK↑, 1, NADH:NAD↑, 1, PPARγ↑, 1, SIRT1↑, 2,

Cell Death ⓘ

Bax:Bcl2↓, 1, Casp1↓, 1, Casp3↓, 1, cl‑Casp3↓, 1, Cyt‑c∅, 1, iNOS↓, 2, p‑JNK↓, 2, MAPK↓, 2, p‑p38↓, 2,

Transcription & Epigenetics ⓘ

cJun↓, 1, p‑cJun↓, 1,

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1, p‑ERK↓, 1, FOXO↑, 1, GSK‐3β↓, 1, STAT3↓, 1,

Migration ⓘ

AntiAg↑, 1, AP-1↓, 1, ARG↑, 1, E-sel↓, 1, MMP9↓, 1, TGF-β1↑, 1, TumCP↓, 1, VCAM-1↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1, NO↓, 2, VEGF↓, 1,

Barriers & Transport ⓘ

BBB↓, 1, BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 3, HMGB1↓, 1, ICAM-1↓, 1, p‑IKKα↓, 1, IL1↓, 1, IL10↑, 3, IL1β↓, 5, IL4↓, 1, IL4↑, 1, IL5↓, 1, IL6↓, 4, Inflam↓, 8, p‑IκB↓, 1, MyD88↓, 1, NF-kB↓, 9, p‑NF-kB↓, 1, p‑p50↓, 1, p65↓, 7, p‑p65↓, 2, PGE2↓, 2, TLR4↓, 2, TLR4∅, 1, TNF-α↓, 7,

Protein Aggregation ⓘ

Aβ↓, 2, NLRP3↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↑, 1, BioAv↝, 1, Dose⇅, 1, eff↑, 4, Half-Life↝, 3,

Clinical Biomarkers ⓘ

ALAT↓, 1, AST↓, 1, BMD↑, 1, BP↓, 1, IL6↓, 4, NOS2↓, 2,

Functional Outcomes ⓘ

cardioP↑, 1, chemoP↑, 1, chemoPv↑, 1, cognitive↑, 1, hepatoP↑, 2, memory↑, 2, motorD↑, 1, neuroP↑, 5, Weight↑, 1,
Total Targets: 106

Scientific Paper Hit Count for: p65, RelA

5 Thymoquinone
4 Curcumin
3 Rosmarinic acid
2 Apigenin (mainly Parsley)
2 Berbamine
2 Fisetin
2 Honokiol
2 Lycopene
2 Propolis -bee glue
2 Piperine
2 Quercetin
2 Resveratrol
2 Shikonin
2 Selenite (Sodium)
1 Baicalein
1 Betulinic acid
1 Carnosic acid
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Celecoxib
1 Celastrol
1 Citric Acid
1 Bicalutamide
1 Oxaliplatin
1 Disulfiram
1 Copper and Cu NanoParticles
1 Ginger/6-Shogaol/Gingerol
1 Luteolin
1 Magnetic Field Rotating
1 Magnetic Fields
1 Oleuropein
1 HydroxyTyrosol
1 Phenethyl isothiocyanate
1 Sulforaphane (mainly Broccoli)
1 Kaempferol
1 Selenium NanoParticles
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#:238  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

p65 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 ⓘ

Protein Aggregation ⓘ

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 ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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