MAPK Cancer Research Results

MAPK, mitogen-activated protein kinase: Click to Expand ⟱

Source: CGL-CS

Type:

Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.

Scientific Papers found: Click to Expand⟱

5142-

AgNPs,

Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells

in-vitro,

CRC,

HUH7

220 and 249 nm

ROS↑, Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis.
Apoptosis↑,
eff↑, Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death
ChemoSen↑, bAgNPs Enhance Cytotoxicity of Chemotherapeutic Drug Cisplatin (CDDP)
EPR↑, The AgNPs were selected over free metal silver for exploration of their anticancerous effects because of the enhanced permeability of NPs into tumors, attributable to the EPR effect.
Casp↑, Induction of Apoptotic Cell Death by bAgNPs through Activation of Caspases
MAPK↑, Our results provide strong evidence for selective activation of MAPK pathways following AgNP exposure

248-

AL,

Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway

in-vitro,

GBM,

U87MG

Bcl-2↓,
BAX↑,
MAPK↑,
ERK↑,
ROS↑, antioxidant prevented inhibitory effect
p38↑,
JNK↑,

249-

AL,

Allicin induces apoptosis of the MGC-803 human gastric carcinoma cell line through the p38 mitogen-activated protein kinase/caspase-3 signaling pathway

in-vitro,

GC,

MGC803

  0.1, 1 and 10 μg/ml

Casp3↑,
p38↑,
BAX↑, up one fold
Bcl-2↓, down 35%
p38↑,
MAPK↑,

241-

AL,

Role of p38 MAPK activation and mitochondrial cytochrome-c release in allicin-induced apoptosis in SK-N-SH cells

in-vitro,

neuroblastoma,

SK-N-SH

 5 μmol/l

 (0, 0.5, 1, 5, 10, and 20 Î¼mol/l) of allicin for 12, 24, and 48 h

Casp3↑,
Casp9↑,
p38↑,
MAPK↑,
Cyt‑c↑, mitochondrial release of cytochrome-c
Apoptosis↑, allicin induced a significant apoptosis compared with the control group

235-

AL,

Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway

in-vitro,

GBM,

U87MG

 90 μM

Apoptosis↑,
Bcl-2↓,
BAX↑,
MAPK↑, mechanisms involved in apoptosis include the mitochondrial pathway, activation of mitogen-activated protein kinases (MAPKs), and caspase cascade and oxidant enzyme system.
p‑ERK↑, In the present study, the level of ERK phosphorylation was increased
ROS↑, ROS are related to allicin-induced apoptosis in the U87MG cells.
eff↓, This study demonstrated that allicin-induced apoptosis was down-regulated by the antioxidant enzyme system

2655-

AL,

Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities

Review,

GC,

TGF-β↓, Allicin can reduce the expression of TGF-2 and its receptor after entering directly into gastric cancer cell
cycD1/CCND1↓, followed by not only downexpression of cyclinD1, cyclinE, and cyclin-dependent kinase (CDK),
cycE/CCNE↓,
CDK1↓, cyclin-dependent kinase (CDK)
DNAdam↑, but also causing DNA damage and generating ROS
ROS↑,
BAX↑, Allicin increases the levels of Bax (proapoptotic protein), Bcl-2 (antiapoptotic protein), and JNK
JNK↑,
MMP↓, through reduction in outer mitochondrial membrane potential
p38↑, allicin induces p38 mitogen that could induce the protein kinase (MAPK) and then increase the expression of Fas binding to Fas ligand (Fas L) and finally activate death pathway through activation of cyt C and caspase-8.
MAPK↑,
Fas↑,
Cyt‑c↑,
Casp8↑,
PARP↑, allicin makes caspase-dependent apoptosis through elevating PARP, caspase-3 and caspase-9, which are mediated by enhanced discharging of mitochondria cyt C to the cytosol.
Casp3↑,
Casp9↑,
Ca+2↑, allicin induces apoptosis via increasing the amounts of free Ca2+, ER stress.
ER Stress↑,
P21↑, generating ROS to produce p21 and phospho-p53 (Ser15).
CDK2↓, Then p21 suppressed the CDK-4/6/cyclinD complex, P21-PCNA, P21-CDK2, and subsequently reduced cdk1/cyclinB1 complex for G2/M phase cell cycle arrest
CDK6↑,
TumCCA↑,
CDK4↓, Then p21 suppressed the CDK-4/6/cyclinD complex

2658-

AL,

The Toxic Effect Ways of Allicin on Different Cell Lines

Review,

Var,

*antiOx↑, The significant functional act of garlic is its anticancer, antimicrobial, antioxidant, antidiabetic, antifibrinolytic, immune enhancing, antiplatelet collected effect and its possible act in prohibiting cardiovascular illnesses
*AntiAg↑,
*cardioP↑,
Ca+2↑, Sultan et al.[34] stated that allicin is cytotoxic to monocytic leukemia cells (THP-1 cells) and stimulates calcium-linked hemolysis and eryptosis in human red blood cells. Allicin advances calcium grades in cells, reasons to oxidative stress and al
ROS↑, Allicin advances calcium grades in cells, reasons to oxidative stress and also induces CK1a, caspase, p38, mitogen-activated protein kinase
Casp↑,
p38↑,
MAPK↑,
hepatoP↑, Wu et al.[42] clarified that allicin applies hepaprotective action counter to hepatic toxicity of cells
chemoP↑, Throughout with other garlic preparations, aged garlic extract (AGE) has been indicated to have hepatoprotective, immune, improving, anticancer, and chemoprotective actions.

2666-

AL,

Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals

Review,

Var,

Inflam↓, , anti-inflammatory, anti-cancer, and immune-modulatory activities
AntiCan↑,
ROS↑, allicin treatment led to the accumulation of ROS
MAPK↑, activation of MAPK/JNK
JNK↑,
TumAuto↑, of autophagy in non small cell lung cancer (NSCLC) cells.
other↑, autophagy at a low dose of allicin is cytoprotective
Dose↝, whereas a high dose of allicin leads to autophagic cell death.
MALAT1↓, allicin could considerably induce oxidative stress and autophagy to suppress osteosarcoma growth via inactivating the MALAT1-miR-376a-Wnt/β-catenin axis,
Wnt↓,
β-catenin/ZEB1↓,

3272-

ALA,

Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Review,

AD,

*antiOx↑, LA has long been touted as an antioxidant,
*glucose↑, improve glucose and ascorbate handling,
*eNOS↑, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*NRF2↑,
*MMP9↓,
*VCAM-1↓,
*NF-kB↓,
*cardioP↑, used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits,
*cognitive↑,
*eff↓, The efficiency of LA uptake was also lowered by its administration in food,
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies;
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑, LA markedly increases intracellular glutathione (GSH),
*PKCδ↑, PKCδ, LA activates Erk1/2 [92,93], p38 MAPK [94], PI3 kinase [94], and Akt
*ERK↑,
*p38↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN [95],
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, stimulate GLUT4 translocation
*GLUT1↑, LA-stimulated translocation of GLUT1 and GLUT4.
*Inflam↓, LA as an anti-inflammatory agent

3539-

ALA,

Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Review,

AD,

*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c

552-

Anamu,

NaHCO3,

A critical review of the therapeutic potential of dibenzyl trisulphide isolated from Petiveria alliacea L (guinea hen weed, anamu)

Review,

NA,

p‑MAPK↑, hyper-phosphorylation of growth factor induced MAPKinases (erk 1 and erk 2) phosphorylation,
Th1 response↓,
Th2↑,
Albumin↝, The cytotoxic activity of DTS was increased by 70-1000 fold when bound to albumin in vitro.

3156-

Ash,

Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Review,

Var,

MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP/DDIT3↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 Â± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2ârelated factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP/DDIT3↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2/PTGS2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

874-

B-Gluc,

Potential promising anticancer applications of β-glucans: a review

Review,

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

4276-

BA,

Baicalin Attenuates Oxygen–Glucose Deprivation/Reoxygenation–Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron–Astrocyte Cocultures

in-vivo,

Stroke,

Newborn Sprague–Dawley (SD) rats

*BDNF↑, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF).
*neuroP↑, neuroprotective mechanisms of baicalin against oxygen–glucose deprivation/reoxygenation
*TrkB↑, baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK.
*PI3K↑,
*Akt↑,
*MAPK↑,
*ERK↑,
*NO↓, elevation of NO and MDA was significantly attenuated by BCL treatment.
*MDA↓,
*SOD↑, BCL treatment increased the expression level of SOD
*TNF-α↓, OGD/R treatment significantly increased the expression levels of TNF-α, IL-1β, and IL-6 (p < 0.01). Compared with that in the OGD/R group, BCL robustly reduced the release of inflammatory cytokines
*IL1β↓,
*IL6?,

2691-

BBR,

Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells

in-vitro,

Oral,

tumCV↓, viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner.
DNAdam↑, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation.
Casp3↑, caspase-3 and -7 activation, and an increase in apoptosis were observed.
Casp7↑,
FasL↑, Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL
Casp8↑, triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP).
Casp9↑,
PARP↑,
BAX↑, Bax, Bad and Apaf-1 were also significantly upregulated by berberine.
BAD↑,
APAF1↑,
MMP2↓, We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK.
MMP9↓,
p‑p38↑, This suggests that berberine-induced activation of the p38 and ERK1/2 MAPK pathways is the principal pathway involved in the apoptosis mediated by berberine in KB cells.
ERK↑,
MAPK↑,

3681-

BBR,

The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology

in-vivo,

AD,

mouse

*memory↑, treatment with berberine significantly improved spatial learning and memory in mice with cognitive decline induced by D-gal
*cognitive↑,
MAPK↑, core targets of berberine for improving cognitive function, include Mapk1, Src, Ctnnb1, Akt1, Pik3ca, Tp53, Jun, and Hsp90aa1.
*Akt↑,
*PI3K↑, PI3K-Akt signaling pathway and MAPK signaling pathway were significantly enriched.
*TP53↑, Tp53 and Jun expression showed a decreasing trend and were significantly lower in the BBR-H group
*Jun↓,
*HSP90↑, src, Ctnnb1, Akt1, Pik3ca, and Hsp90aa1 exhibited an increasing tendency in both the BBR-L and BBR-H groups
*neuroP↑, Akt1, Ctnnb1, Tp53, and Jun were involved in the neuroprotective actions of berberine.
*Inflam↓, pharmacological effects of BBR, including anti-inflammatory
*antiOx↑, BBR has antioxidant properties as well as protective effects against neurodegenerative diseases
*p16↓, BBR reduces the expression of P16 in brain tissue of cognitive dysfunctions mice
*ER Stress↓, inhibition of endoplasmic reticulum stress

5591-

BetA,

Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment

Review,

BC,

IC50 values ranging from 1 to 13.0 μg mL−1

BioAv↓, However, its poor water solubility limits its optimal therapeutic potential.
BioAv↑, nano-drug delivery systems (NDDSs) have gained significant attention as a method to substantially improve low solubility and poor drug bioavailability, enhance targeted drug delivery, and reduce side effects.
selectivity↑, reviews by Simone Fulda23,24 strengthened BA's potential for cancer treatment and prevention, particularly its ability to selectively trigger apoptosis in cancer cells while causing minimal harm to normal cells.
eff↑, It is important to note that the anticancer effects of BA on different types of tumors are more potent at a pH lower than 6.8.34
angioG↓, figure 3
*antiOx↑,
*Inflam↓,
MMP↓, BA-induced mitochondrial depolarization
Bcl-2↓, BA treatment has been shown to lower Bcl-2 expression and increase Bax, resulting in the activation of caspase-9 and caspase-3 through the mitochondrial pathway.63
BAX↑,
Casp9↑,
Casp3↑,
GRP78/BiP?, BA directly targets GRP78, triggering ER stress by activating the PERK-eIF2α-CHOP apoptotic cascade
ER Stress↑,
PERK↑,
CHOP/DDIT3↑,
ChemoSen↑, BA's ability to chemosensitize BC cells to taxanes highlights its importance in situations of drug resistance
SESN2↑, Under hypoxia, BA strongly increases SESN2 expression.
ROS↑, Reducing SESN2 levels enhances BA-induced ROS production, DNA damage, and radiosensitivity, while decreasing autophagic flux, indicating that SESN2-mediated autophagy serves as a protective adaptive response.68
MOMP↓, decreases the mitochondrial outer membrane potential (MOMP),
MAPK↑, This leads to the activation of p38 Mitogen-activated protein kinase (p38 MAPK), the release of cytochrome C, apoptosis-inducing factor (AIF),
Cyt‑c↑,
AIF↑,
STAT3↓, BA suppresses the signal transducer and activator of transcription (STAT) 3 signaling pathways
FAK↓, BA's inhibition of STAT3, as well as FAK, leads to decreased expression of MMPs and elevated TIMP-2, thereby impairing cancer cell migration and invasion
TIMP2↑,
TumCMig↓,
TumCI↓,
Sp1/3/4↓, Sp inhibition reduces cancer gene expression, inhibiting cancer cell growth.
TumCCA↑, It increases cell numbers in the G2/M phase, leading to cell cycle arrest.
DNAdam↑, causes DNA damage, thereby inhibiting the progression and invasion of cancer cells.

2743-

BetA,

Betulinic acid and the pharmacological effects of tumor suppression

Review,

Var,

ROS↑, BA improves the level of reactive oxygen species (ROS) production and alters the mitochondrial membrane potential gradient, followed by the release of cytochrome c (Cyt c), which causes the mitochondrial-mediated apoptosis of tumor cells via a caspas
MMP↓,
Cyt‑c↑,
Apoptosis↑,
TumCCA↑, BA can inhibit cancer cell growth and proliferation via cell cycle arrest
Sp1/3/4↓, BA, can inhibit the protein expression of Sp1, Sp2 and Sp4 through the microRNA (miR)-27a-ZBTB10-Sp1 axis
STAT3↓, BA can downregulate the activation of STAT3 through the upregulation of Src homology 2 domain-containing phosphatase 1 (SHP-1)
NF-kB↓, NF-κB can be inhibited by reducing the activation of inhibitor of NF-κB (IκBα) kinase (IKKβ) and phosphorylation of IκBα with BA
EMT↓, nvasion and metastasis of malignancies is prevented via epithelial-mesenchymal transition (EMT) and inhibition of topoisomerase I
TOP1↓,
MAPK↑, BA leads to the activation, via phosphorylation, of pro-apoptotic MAPK proteins, P38 and SAP/JNK, the formation of ROS and the upregulation of caspase
p38↑,
JNK↑,
Casp↑,
Bcl-2↓, BA downregulates Bcl-2 and upregulates the Bax gene in HeLa cell lines
BAX↑,
VEGF↓, BA can decrease the expression of VEGF via Sp proteins, thus having an antiangiogenic role
LAMs↓, BA suppresses the expression of lamin B1 in pancreatic cancer cells

5482-

BM,

Bacopa monnieri protects SH-SY5Y cells against tert-Butyl hydroperoxide-induced cell death via the ERK and PI3K pathways

in-vitro,

Nor,

*neuroP↑, The neuroprotective effect of BM was evaluated
*ERK↑, BM by activation of ERK/MAPK and PI3K/Akt signaling pathways protects SH-SY5Y cells from TBHP-induced cell death.
*Akt↑,
*MAPK↑,
*PI3K↑,
*Inflam↓, Mechanistically, BM has been reported to have anti-inflammatory, anti-depressant and antioxidant effects9–12
antiOx↑, enhancement of antioxidant enzymes

2767-

Bos,

The potential role of boswellic acids in cancer prevention and treatment

Review,

Var,

*Inflam↓, profound application as a traditional remedy for various ailments, especially inflammatory diseases including asthma, arthritis, cerebral edema, chronic pain syndrome, chronic bowel diseases, cancer
AntiCan↑,
*MAPK↑, 11-keto-BAs can stimulate Mitogen-activated protein kinases (MAPK) and mobilize the intracellular Ca(2+) that are important for the activation of human polymorphonuclear leucocytes (PMNL)
*Ca+2↝,
p‑ERK↓, AKBA prohibited the phosphorylation of extracellular signal-regulated kinase-1 and -2 (Erk-1/2) and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB
TumCI↓,
cycD1/CCND1↓, In the case of colon cancer, BA treatment on HCT-116 cells led to a decrease in cyclin D, cyclin E, and Cyclin-dependent kinases such as CDK2 and CDK4, along with significant reduction in phosphorylated Rb (pRb)
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p‑RB1↓,
*NF-kB↓, convey inhibition of NF-kappaB and subsequent down-regulation of TNF-alpha expression in activated human monocytes
*TNF-α↓,
NF-kB↓, PC-3 prostate cancer cells in vitro and in vivo by inhibiting constitutively activated NF-kappaB signaling by intercepting the activity of IkappaB kinase (IKK
IKKα↓,
MCP1/CCL2↓, LPS-challenged ApoE-/- mice via inhibition of NF-ÎºB and down regulation of MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF
IL1α↓,
MIP2↓,
VEGF↓,
Tf↓,
COX2/PTGS2↓, pancreatic cancer cell lines, AKBA inhibited the constitutive expression of NF-kB and caused suppression of NF-kB regulated genes such as COX-2, MMP-9, CXCR4, and VEGF
MMP9↓,
CXCR4↓,
VEGF↓,
eff↑, AKBA and aspirin revealed that AKBA has higher potential via modulation of the Wnt/Î²-catenin pathway, and NF-kB/COX-2 pathway in adenomatous polyps
PPARα↓, AKBA is also responsible for down-regulation of PPAR-alpha and C/EBP-alpha in a dose and temporal dependent manner in mature adipocytes, ultimately leading to pparlipolysis
lipid-P?,
STAT3↓, activation of STAT-3 in human MM cells could be inhibited by AKBA
TOP1↓, (PKBA; a semisynthetic analogue of 11-keto-Î²-boswellic acid), had been reported to influence the activity of topoisomerase I & II,
TOP2↑,
5HT↓, (5-LO), responsible for catalyzing the synthesis of leukotrienes from arachidonic acid and human leucocyte elastase (HLE), and serine proteases involved in several inflammatory processes, is considered to be a potent molecular target of BA derivative
p‑PDGFR-BB↓, BA up-regulates SHP-1 with subsequent dephosphorylation of PDGFR-Î² and downregulation of PDGF-dependent signaling after PDGF stimulation, thereby exerting an anti-proliferative effect on HSCs hepatic stellate cells
PDGF↓,
AR↓, AKBA targets different receptors that include androgen receptor (AR), death receptor 5 (DR5), and vascular endothelial growth factor receptor 2 (VEGFR2), and leads to the inhibition of proliferation of prostate cancer cells
DR5↑, induced expression of DR4 and DR5.
angioG↓, via apoptosis induction and suppression of angiogenesis
DR4↑,
Casp3↑, AKBA resulted in activation of caspase-3 and caspase-8, and initiation of poly (ADP) ribose polymerase (PARP) cleavage.
Casp8↑,
cl‑PARP↑,
eff↑, AKBA was preincubated with LY294002 or wortmannin (inhibitors of PI3K), it caused a significant enhancement of apoptosis in HT-29 cells
chemoPv↑, chemopreventive response of AKBA was estimated against intestinal adenomatous polyposis through the inhibition of the Wnt/Î²-catenin and NF-ÎºB/cyclooxygenase-2 signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
ascitic↓, AKBA by the suppression of ascites,
Let-7↑, AKBA could up-regulate the expression of let-7 and miR-200
miR-200b↑,
eff↑, anti-tumorigenic effects of curcumin and AKBA on the regulation of specific cancer-related miRNAs in colorectal cancer cells, and confirmed their protective action
MMP1↓, . It can inhibit the expression of MMP-1, MMP-2, and MMP-9 mRNAs along with secretions of TNF-Î± and IL-1Î² in THP-1 cells.
MMP2↓,
eff↑, combined administration of metformin, an anti-diabetic drug, and boswellic acid nanoparticles exhibited significant synergism through the inhibition of MiaPaCa-2 pancreatic cancer cell proliferation
BioAv↓, BA as a therapeutic drug is its poor bioavailability
BioAv↑, administration of BSE-018 concomitantly with a high-fat meal led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA)
Half-Life↓, drug needs to be given orally at the interval of six hours due to its calculated half- life, which was around 6 hrs.
toxicity↓, BSE has been found to be a safe drug without any adverse side reactions, and is well tolerated on oral administration.
Dose↑, Boswellia serrata extract to the maximum amount of 4200 mg/day is not toxic and it is safe to use though it shows poor bioavailability
BioAv↑, Approaches like lecithin delivery form (PhytosomeÂ®), nanoparticle delivery systems like liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly (lactic-co-glycolic acid) nanoparticles
ChemoSen↑, Like any other natural products BA can also be effective as chemosensitizer

5693-

BRU,

Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2

in-vivo,

HCC,

mouse Hepa-1c1c7 hepatoma cells

NRF2↓, we show that brusatol provokes a rapid and transient depletion of Nrf2 protein
eff↑, brusatol is capable of sensitizing mammalian cells to chemical stress.
p‑MAPK↑, brusatol provoked a rapid increase in the phosphorylation of p38 MAPK, AKT, ERK1/2, and JNK1/2 in parallel with depletion of Nrf2
p‑Akt↑,
p‑ERK↑,
p‑JNK↑,

5697-

BRU,

Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous Cell Carcinoma

in-vitro,

HNSCC,

NRF2↓, Brusatol, a Nrf2 Inhibitor
STAT3↓, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells.
proCasp3↑, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells.
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Hif1a↓, BT also induced the degradation of HIF-1α
cMyc↓, BT suppressed c-Myc expression
JNK↑, BT was found to activate JNK and p38 MAPK pathways with concurrent inhibition of proinflammatory signaling pathways such as NF-κB and STAT3
MAPK↑,
tumCV↓, BT Reduced the Cell Viability of HNSCC Cells
ROS∅, BT treatment did not significantly alter the level of ROS

1651-

CA,

PBG,

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Review,

Var,

Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 Î¼M) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

6010-

CGA,

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

Review,

Nor,

*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP/DDIT3↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2/PTGS2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

6138-

CHr,

Cisplatin,

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

in-vivo,

Nor,

Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil.

*toxicity↝, it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury.
eff↑, Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage.
chemoP↑,
*ROS↓, protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage
*MAPK↑,
*P53↑,
GSH↓, chrysin induces cancer cell death synergistically with doxorubicin by chemosensitizing these cells to chemotherapy via GSH depletion within the cancer cells

2780-

CHr,

Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review

Review,

Var,

*antiOx↑, antioxidant (13), anti-inflammatory (14), antibacterial (15), anti-hypertensive (16), anti-allergic (17), vasodilator (18),
Inflam↓,
*hepatoP↑, anti-diabetic (19), anti-anxiety (10), anti-viral (20), anti-estrogen (21), liver protective (22), anti-aging (23), anti-seizure (24), and anti-cancer effects (25)
AntiCan↑,
Cyt‑c↑, (1) facilitating the release of cytochrome C from the mitochondria,
Casp3↑, (2) activating caspase-3 and inhibiting the activity of the XIAP molecule,
XIAP↓,
p‑Akt↓, (3) reducing AKT phosphorylation and triggering the PI3K pathway and induction of apoptosis
PI3K↑,
Apoptosis↑,
COX2/PTGS2↓, chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2.
FAK↓, ESCC cells: resultant blockage of the FAK/AKT signaling pathways
AMPK↑, A549: activation of AMPK by chrysin contributes to Akt suppression
STAT3↑, 4T1cell: inhibited STAT3 activation
MMP↓, Chrysin induces apoptosis through the intrinsic mitochondrial pathway that disrupts mitochondrial membrane potential (MMP) and increases DNA fragmentation.
DNAdam↑,
BAX↑, produces pro-apoptotic proteins, including Bax and Bak, and activates caspase-9 and caspase-3 in various cancer cells
Bak↑,
Casp9↑,
p38↑, chrysin can inhibit tumor growth by activating P38 MAPK and stopping the cell cycle
MAPK↑,
TumCCA↑,
ChemoSen↑, beneficial in inhibiting chemotherapy resistance of cancer cells
HDAC8↓, chrysin suppresses tumorigenesis by inhibiting histone deacetylase 8 (HDAC8)
Wnt↓, chrysin can attenuate Wnt and NF-κB signaling pathways
NF-kB↓,
angioG↓, chrysin can inhibit angiogenesis and inducing apoptosis in HTh7 cells, 4T1 mice, and MDA-MB-231 cells
BioAv↓, low bioavailability of flavonoids such as chrysin

2791-

CHr,

Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction

in-vitro,

Ovarian,

OV90

TumCP↓, chrysin inhibited ovarian cancer cell proliferation and induced cell death by increasing reactive oxygen species (ROS) production and cytoplasmic Ca2+ levels as well as inducing loss of mitochondrial membrane potential (MMP).
TumCD↑,
ROS↑,
Ca+2↑,
MMP↓,
MAPK↑, chrysin activated mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in ES2 and OV90 cells in concentration-response experiments
PI3K↑, results indicate that the chrysin-induced activation of PI3K and MAPK signaling molecules, which induced apoptosis,
p‑Akt↑, Chrysin stimulated the phosphorylation of AKT and P70S6K proteins in both ES2 and OV90 cells compared to the untreated control cell
PCNA↓, treatment with chrysin attenuated the abundant expression of PCNA protein in both ES2 and OV90 cells
p‑p70S6↑,
p‑ERK↑, chrysin activated the phospho-ERK1/2, p38, and JNK proteins as members of the MAPK pathway in the ovarian cancer cells
p38↑,
JNK↑,
DNAdam↑, stimulates apoptotic events in prostate cancer cells by the accumulation of DNA fragmentation, an increase in the population of cells in the sub-G1 phase of the cell cycle
TumCCA↑,
chemoP↑, combination therapy with chrysin enhances the therapeutic effect of the chemotherapeutic agent, docetaxel, in lung cancer by reducing its adverse effects

2792-

CHr,

Chrysin induces death of prostate cancer cells by inducing ROS and ER stress

in-vitro,

Pca,

DU145

0, 5, 10, 20, 50 and 100 Î¼M

in-vitro,

Pca,

PC3

DNAdam↑, chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle
TumCCA↑,
MMP↓, chrysin induced loss of mitochondria membrane potential (MMP), while increasing production of reactive oxygen species (ROS) and lipid peroxidation in a dose-dependent manner
ROS↑,
lipid-P↑,
ER Stress↑, Also, it induced endoplasmic reticulum (ER) stress through activation of unfolded protein response (UPR) proteins including PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78)
UPR↑,
PERK↑,
eIF2α↑,
GRP78/BiP↑,
PI3K↓, chrysin-mediated intracellular signaling pathways suppressed phosphoinositide 3-kinase (PI3K) and the abundance of AKT, P70S6K, S6, and P90RSK proteins, but stimulated mitogen-activated protein kinases (MAPK) and activation of ERK1/2 and P38 proteins
Akt↓,
p70S6↓,
MAPK↑,

6183-

Cu,

Copper(II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response

in-vitro,

Liver,

HepG2

ROS↑, Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species.
MAPK↑, CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1.
ERK↑,
AP-1↑,

1571-

Cu,

Copper in cancer: From pathogenesis to therapy

Review,

NA,

*toxicity↝, The toxicity of Cu overload is known to be due, in part, to the release of ROS via the Fenton or Haber-Weiss reaction, causing lipid, protein, DNA, and RNA damage
ROS↑, Cu-induced ROS can induce lipid peroxidation, which raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic.
lipid-P↓,
HNE↑, raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic
MAPK↑, Cu exposure causes an elevation in intracellular ROS levels, which then stimulates the MAPK signaling pathway, increasing JNK/SAPK and p38 homologous activity and phosphorylation levels
JNK↑, Cu-induced ROS continuously activate JNK, promote the production of the AP-1 transcription factor, increase Beclin 1 and Atg7 production, and cause autophagy and apoptosis in tumor cells
AP-1↑,
Beclin-1↑,
ATG7↑,
TumAuto↑,
Apoptosis↑,
HO-1↑, Fang and colleagues consistently found that Cu activates the ROS/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase-1 (NQO1) signaling cascade to induce autophagy
NQO1↑,
mt-ROS↑, Cu NPs induce complete autophagy by enhancing mitochondrial ROS production and inducing autophagy
Fenton↑, generating large amounts of ROS and oxygen via a Fenton-like reaction

167-

CUR,

Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria

in-vitro,

Pca,

PC3

MAPK↑,
JNK↑,
Casp3↑, Caspase-3, caspase-8, and caspase-9 were activated, and cytochrome c and apoptosis-inducing factor (AIF) were released from mitochondria following curcumin treatment
Casp8↑,
Casp9↑,
AIF↑, released from mitochondria
GSH↓, Curcumin treatment of PC3 cells caused time- and dose-dependent induction of apoptosis and depletion of cellular reduced glutathione (GSH).
eff↓, Exogenous GSH and its precursor N-acetyl-cysteine, but not ascorbic acid (AA) or ebselen, decreased curcumin accumulation in PC3 cells and also prevented curcumin-induced DNA fragmentation.
Apoptosis↑, Curcumin Triggers Apoptosis in Prostate Cancer Cells
DNAdam↑, curcumin-induced DNA fragmentation in PC3 cells was prevented in the presence of exogenous GSH or NAC.

6720-

CUR,

SFN,

DHCA,

Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid against Human Colon Cancer Cells

in-vitro,

Colon,

HT29

in-vitro,

Colon,

Caco-2

in-vitro,

Nor,

FHC

selectivity↑, SD(1:1) was significantly more cytotoxic for cancer cells than healthy cells,
TumCCA↑, At a dose of 15 µM, sulforaphane caused cell-cycle arrest at G2/M phase and apoptosis in a dose-dependent manner in HT-29
Apoptosis↑,
ROS↑, Jaganathan [46] reported an increase in ROS by caffeic acid in HCT 15 colon cancer cells, which caused a reduction in mitochondrial membrane potential and consequently apoptosis.
MMP↓,
ROS⇅, action of dihydrocaffeic acid could be a hormetic mechanism, where, at high doses, it causes oxidative damage, causing mitochondrial dysfunction and apoptosis.
ERK↑, The high amount of ROS unleashed a chain of events, including activation of ERK, JNK, and p38 MAPK pathways, which in turn induced p21 and downregulated cyclin D1, causing cell-cycle arrest at G1 phase.
JNK↑,
MAPK↑,
P21↑,
cycD1/CCND1↓,
Cyt‑c↑, facilitating pore opening and subsequent cytochrome c release, resulting in the activation of the apoptotic intrinsic pathway.

7442-

CYN,

Cynaropicrin induces the apoptosis of colorectal cancer cells by elevating reactive oxygen species and activating the JNK/p38 MAPK

in-vitro,

CRC,

HCT116

Apoptosis↑, Cynaropicrin also induced apoptosis, as identified by an Annexin V-FITC/PI double staining, and this apoptosis was accompanied by the phosphorylations of JNK and p38 MAPK
p‑JNK↑,
p‑MAPK↑,
ROS↑, cynaropicrin increased reactive oxygen species (ROS) levels
eff↓, and N-acetylcysteine(NAC) pretreatment confirmed ROS mediated the cytotoxicity of cynaropicrin.
TumCCA↑, cynaropicrin induced cell cycle arrest at the G2/M phase by modulating cell cycle regulators,
Bcl-2↓, cynaropicrin altered the balance of Bcl-2 family proteins.

7438-

CYN,

Cynaropicrin Suppresses Cell Proliferation by Inducing Mitophagy through p38 MAPK-Mediated Mitochondrial ROS Generation in Human Hepatocellular Carcinoma Cells

in-vitro,

HCC,

tumCV↓, cynaropicrin significantly induced cytotoxicity and autophagy in HCC cells, but not in immortalized non-cancerous hepatocytes,
TumAuto↑,
selectivity↑,
mt-ROS↑, which was related to the generation of mitochondrial reactive oxygen species (mtROS) and induction of mitochondrial membrane potential loss.
MMP↓,
LC3B↑, Under cynaropicrin treatment, the expression of microtubule-associated protein light chain 3, which is involved in the elongation of the phagophore membrane, was upregulated
Beclin-1↓, whereas the expression of Beclin-1 and p62, which are essential for the formation of autophagosomes, was downregulated.
p62↓,
PINK1↑, expression of mitophagy regulators PTEN-induced kinase 1 (PINK1) and Parkin in the mitochondria increased, suggesting the induction of autophagic flux in the mitochondria.
PARK2↑,
eff↓, However, N-acetyl-l-cysteine(NAC), a ROS scavenger, counteracted cynaropicrin-induced effects.
p‑MAPK↑, cynaropicrin increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the p38 MAPK inhibitor, SB203580, specifically attenuated cynaropicrin-induced cytotoxicity and mtROS production.

6823-

EMD,

Role of emodin to prevent gastrointestinal cancers: recent trends and future prospective

Review,

Var,

AntiCan↑, Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural compound derived from traditional Chinese and Japanese medicine, has recently garnered significant attention for its potential anticancer properties.
*antiOx↑, Emodin exerts its chemoprotective effects through a combination of antioxidative, anti-inflammatory, and anti-proliferative mechanisms.
*chemoP↑,
*Inflam↓,
TumCP↓,
TumMeta↓, emodin inhibits cancer metastasis, disrupts cell cycle progression, and impairs cancer cell survival.
TumCCA↑,
MAPK↑, activation of the p38 MAPK/JNK1/2 signaling pathway, the upregulation of pro-apoptotic factors such as Bax/Bcl-2 and caspases, and the enhancement of reactive oxygen species (ROS) levels (
BAX↑,
Casp↑,
ROS↑,
*BioAv↓, The pharmacokinetic limited properties of emodin significantly affect its bioavailability and bioactivity, hence limiting its therapeutic uses.
other↝, Chinese medicinal herbs contains emodin, which is utilized in traditional Chinese and Japanese medicine, include Rheum palmatum, Polygonum cuspidatum, and Cassia obtusifolia
TumCI↓, including as invasion and metastasis, tumour angiogenesis, epithelial-mesenchymal transition (EMT), cell growth (i.e., promotion of apoptosis, reduction of proliferation, and changed cellular redox status).
EMT↓,
TumCG↑,
Apoptosis↑,
TumCP↑,
MMP2↓, inhibit cell invasion by modulating and down regulating the activation and expression of MMP2, Bax/Bcl-2 and caspase-3 involving in esophageal cancer
Casp3↑,
ChemoSen↑, When combined with ciplatin, emodin significantly raises intracellular ROS, which improves proapoptotic effects and can be used to treat esophageal cancer
PI3K↓, figure 3
Akt↓,
Cyt‑c↑,
cl‑PARP↑,
MMP↓, emodin trigger the mitochondria of GI cancer cells to disrupt mitochondrial membrane potential by signaling molecules Bax, Bak PARP and triggers the release of cytochrome c to activate caspase -9 and 3 culminating into apoptosis
Warburg↓, Hepatic carcinoma HepG2 cells 20–200 µM Reduces wadburg effect by ↓ HKII, PKM2, LDHA, limiting energy supply, ↑ ROS production, ↑ mitochondrial damage and apoptosis
HK2↓,
PKM2↓,
LDHA↓,
mtDam↑,
Apoptosis↑,
N-cadherin↓, Ovarian cancer SK-OV-3, A2780, PA-1 2.5–80 µM Inhibited EMT by ↓ N cadherin & vimentin and ↑ E-cadherin
Vim↓,
E-cadherin↑,
eff↑, EMO exhibits broader range of pharmacological activities and in combination with nano range molecules.
eff↑, chitosan oligosaccharide nano-micelles (CSO-SA-EMO) significantly enhanced antioncogenic properties against the gastric cancer cells.
eff↑, Fe3O4- PEG-Cy7-EMO nanoparticles also proved potential nanoplatform in pancreatic tumor xenografted mice.
toxicity↝, emodin treatment at a maximum dose of 80 mg/Kg body weight orally and 40 mg/Kg body weight intraperitoneally does not significantly harm patients.
toxicity↑, emodin dosage higher than 500–1500 mg/Kg of body weight may cause toxicity such as hepatotoxicity and inflammation

6842-

EVO,

Evodiamine activates cellular apoptosis through suppressing PI3K/AKT and activating MAPK in glioma

in-vitro,

GBM,

U251

in-vitro,

GBM,

LN229

TumCP↓, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner.
ROS↑, Moreover, Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption.
MMP↓,
PI3K↓, suppressing PI3K/AKT signaling and inducing MAPK phosphorylation (p38 and JNK, but not ERK) to regulate apoptotic proteins (Bax, Bcl-2, Cytochrome c, Caspase-3, and PARP).
Akt↓,
p‑MAPK↑, Evo activated the MAPK pathway
cl‑Casp3↑, Cleaved Caspase-3 and cleaved PARP were expressed at higher levels in Evo-treated cells than control cells

2830-

FIS,

Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent

Review,

Var,

TumCG↓, suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration.
angioG↓,
*ROS↓,
TumCMig↓,
VEGF↓, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1.
MAPK↑, including the activation of MAPK. activation of MAPK is crucial for mediating cancer cell proliferation, apoptosis, and invasion
NF-kB↓, ability of fisetin to suppress NF-κB activity has been demonstrated in various diseases
PI3K↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT
Akt↓,
mTOR↓, Fisetin has been shown to be effective against PI3K expression, AKT phosphorylation, and mTOR activation in various cancer cells,
NRF2↑, effects of fisetin on the activation of Nrf2 and upregulation of HO-1 have been demonstrated in various diseases
HO-1↑,
ROS↓, Liver cancer Resist proliferation, migration and invasion, induce apoptosis, attenuate ROS and inflammation
Inflam↓,
ER Stress↑, Oral cancer Induce apoptosis and autophagy, promote ER stress and ROS, suppress proliferation
ROS↑, Multiple studies have demonstrated that fisetin has the ability to induce apoptosis in cancer cells, and various mechanisms are involved, including the activation of MAPK, NF-κB, p53, and the generation of reactive oxygen species (ROS)
TumCP↓,
ChemoSen↑, Breast cancer Promote apoptosis and invasion and metastasis, enhance chemotherapeutic effects
PTEN↑,
P53↑, activation of MAPK, NF-κB, p53,
Casp3↑,
Casp8↑,
Casp9↑,
COX2/PTGS2↓, fisetin inhibits COX2 expression
Wnt↓, regulating a number of important angiogenesis-related factors in cancer cells, such as VEGF, MMP2/9, eNOS, wingless and Wnt-signaling.
EGFR↓,
Mcl-1↓,
survivin↓, fisetin interferes with NF-κB signaling, resulting in the reduction of survivin, TRAF1, Bcl-xl, Bcl-2, and IAP1/2 levels, ultimately inhibiting apoptosis
IAP1↓,
IAP2/BIRC3↓,
PGE2↓, fisetin inhibits COX2 expression, leading to the down-regulation of PGE2 secretion and inactivation of β-catenin, thereby inducing apoptosis
β-catenin/ZEB1↓,
DR5↑, fisetin markedly induces apoptosis in renal carcinoma through increased expression of DR5, which is regulated by p53.
MMP2↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT and JNK pathways, resulting in the suppression of MMP-2 and MMP-9 expression
MMP9↓,
FAK↓, fisetin can inhibit cell migration and reduce focal adhesion kinase (FAK) phosphorylation levels
uPA↓, fisetin significantly suppresses the invasion of U-2 cells by decreasing the expression of NF-κB, urokinase-type plasminogen activator (uPA), FAK, and MMP-2/9
EMT↓, Fisetin has been shown to have the ability to reverse EMT, thereby inhibiting the invasion and migration of cancer cells
ERK↓, fisetin has the ability to suppress ERK1/2 activation and activate JNK/p38 pathways
JNK↑,
p38↑,
PKCδ↓, fisetin reduces the expression of MMP-9 by inhibiting PKCα/ROS/ERK1/2 and p38 MAPK activation
BioAv↓, low water solubility of fisetin poses a significant challenge for its administration, which can limit its biological effects
BioAv↑, Compared to free fisetin, fisetin nanoemulsion has demonstrated a 3.9-fold increase in the generation of reactive oxygen species (ROS) and induction of apoptosis, highlighting its enhanced efficacy
BioAv↑, Liposomal encapsulation has shown potential in enhancing the anticancer therapeutic effects of fisetin

6963-

Form,

Formononetin-induced apoptosis by activation of Ras/p38 mitogen-activated protein kinase in estrogen receptor-positive human breast cancer cells

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF7

in-vitro,

BC,

T47D

eff↝, Its pharmacological effects in vivo may be either estrogenic or anti-estrogenic, mainly depending upon the estrogen levels.
TumCP↓, formononetin inhibited the proliferation of ER-positive MCF-7 cells and T47D cells.
TumCP∅, In contrast, formononetin could not inhibit the cell of growth of ER-negative breast cancer cells such as MDA-MB-435 S cells.
MAPK↑, formononetin activated MAPK signaling pathway in a dose-dependent manner, which resulted in the increased ratio of Bax/Bcl-2, and induced apoptosis on MCF-7 cells.
Bax:Bcl2↑,
Apoptosis↑,

7019-

Fuc,

Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43

vitro+vivo,

HCC,

HUH7

TumCI↓, Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPK-dependent NDRG-1/CAP43 and partly, under normoxic conditions, through up-regulation of p42/44 MAPK-dependent VMP-1 expression.
p42↑,
p44↑,
MAPK↑,
TumMeta↓, It also significantly decreased liver metastasis in vivo
hepatoP↑, As regards its hepatoprotective effect, fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8, and -7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain (FADD) into the dea
*antiOx↑, Fucoidan has also been reported to exert a protective effect on hepatocytes showing anti-oxidative effects against acute liver injury and liver fibrosis
*TumCP↓, Cell proliferation following fucoidan treatment decreased in a dose-dependent manner under both normoxic and hypoxic conditions
Vim↓, fucoidan treatment was found to decrease the expressions of vimentin, E-cadherin, and fibronectin in Huh-7 cells as compared to controls
E-cadherin↓,
Fibronectin↓,
NDRG1↑, Fucoidan enhances the expression of NDRG-1/CAP43 by the p42/44 MAPK pathway
VMP-1↑, Enhanced expression of VMP-1 by fucoidan under normoxic conditions
TumMeta↓, Fucoidan inhibited liver metastasis in an intrahepatic portal vein metastasis model in vivo

7006-

Fuc,

Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug—A Review

Review,

Var,

*toxicity↓, Fucoidan is a versatile, nontoxic marine-origin heteropolysaccharide that has received much attention due to its beneficial biological properties and safety.
*AntiViral↑, ucoidan has been demonstrated to exhibit a variety of conventional bioactivities, such as antiviral, antioxidant, and immune-modulatory characteristics, and anticancer activity against a wide range of malignancies has also recently been discovered.
*antiOx↑,
*Imm⇅,
AntiCan↑,
TumCCA↑, Fucoidan inhibits tumorigenesis by prompting cell cycle arrest and apoptosis, blocking metastasis and angiogenesis, and modulating physiological signaling molecules.
Apoptosis↑,
TumMeta↓,
angioG↓,
antiNeop↑, Fucoidans’ capacity to bind to Toll-like receptors and intervene with the action of vascular endothelial growth factors (VEGF) and matrix metalloproteinases (MMPs) could explain their anti-neoplastic properties
VEGF↓,
MMPs↓,
BioAv↑, Low molecular weight fractions (LMWF), in particular, are thought to be more biocompatible [47]
BioAv↑, in rats, following topical administration of fucoidan (MW 750 kDa) from Fucus vesiculosus demonstrated fine skin-penetrating characteristics.
ROS⇅, Induction/inhibition of reactive oxygen species (ROS), mitochondrial instability, and caspase and poly (ADP-ribose) polymerase (PARP) cleavage are all aspects of it
cl‑PARP↑, fucoidan treatment causes PARP cleavage and caspase-3/7 activation in MCF-7 cells, which are hallmarks of apoptosis [
Casp3↑,
Casp7↑,
ROS↑, human hepatoma SMMC-7721 cells, fucoidan therapy caused noteworthy growth inhibition and ROS-mediated apoptosi
GSH↓, lower glutathione consumption (GSH), mitochondrial swelling, and depolarization of the mitochondrial membrane potential
MMP↓,
PI3K↓, Fucoidan inhibits PI3K, suppressing ERK and activates MAPK, limiting cancer cell proliferation and decreasing Bcl-2 to Bax ratio, inducing caspase-dependent apoptosis in BEL-7402 and LM3 cell lines
ERK↓,
MAPK↑,
TumCP↓,
Bax:Bcl2↑,
TJ↑, Meanwhile, dietary fucoidan progressively restores intestinal villi by upregulating the expression of tight junction proteins such as ZO-1, Occludin, Claudin-1, and Claudin-8 via p38 MAPK and ERK1/2 activation.
ZO-1↑,
OCLN↑,
CLDN1↑,
IBI↑, fucoidan supplementation improves intestinal barrier function by enhancing intestinal microbiota diversity
GutMicro↑,
NK cell↑, ↑NK cell-mediated anticancer immunity
STAT3↓, Inhibits STAT3 Signaling
eff↑, Astragalus polysaccharide as a topical mucosal adjuvant to boost the anticancer efficacy of immune checkpoint inhibitors

4302-

Gins,

Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease

Review,

AD,

*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE/β-secretase↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

2082-

HNK,

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

in-vitro,

GBM,

U87MG

36.27 μM

In U87-MG cells, the optimum concentration of honokiol was 20 µM, and the optimum time was 48 h

in-vitro,

GBM,

U251

59.53 μM

n U251-MG cells, the optimum concentration of honokiol was 40 µM, and the optimum time was 48 h

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

7528-

HT,

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity

NA,

Jurkat

27.3 µg·mL−1

NA,

HL-60

109.8 µg·mL−1

NA,

RAW264.7

45.7 µg·mL−1

*antiOx↑, Hydroxytyrosol (HT), the main representative of polyphenols of olive oil, has been described as one of the most powerful natural antioxidants, also showing anti-inflammatory, antimicrobial, cardioprotective and anticancer activity in different type o
*Inflam↓, HT acts as an anti-inflammatory agent, reducing NO levels in Raw264.7 cells previously stimulated by lipopolysaccharide (LPS).
*AntiBio↑,
*cardioP↑,
AntiCan↑,
TumCCA↑, HT caused cell arrest in G0/G1 phase in both Jurkat and HL60 cells by increasing G0/G1 phase and significantly decreasing S phase.
PI3K↓, HT inhibited the PI3K signaling pathway and, consequently, the MAPK pathway was activated.
MAPK↑,
ROS↑, Hydroxytyrosol Increases ROS Production in Jurkat and HL60 Cells
Apoptosis↑, HL60 cells, hydroxytyrosol administration resulted in increased cell apoptosis as a consequence of increased caspase-9 levels and a significant decrease in Bcl2 and phospho-p53
Casp9↑,
Bcl-2↓,
p‑P53↓,

7565-

HYP,

Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review

Review,

AD,

*Inflam↓, exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects,
*antiOx↑,
*neuroP↑,
*lipid-P↓, Anti-oxidant Saccharomyces Cerevisiae 5, 20 mg/L Decreased LPO and the level of ROS
*ROS↓,
*IL1β↓, HT22 cells 20 μM Alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF.
*IL6↓,
*IL8↓,
*TNF-α↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Catalase↑,
*SOD↑,
*GSH↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*BDNF↑, Male Albino Swiss mice 0.94 mg/kg, 3.75 mg/kg Mediated by monoaminergic system and the upregulation of BDNF level
*NF-kB↓, Inhibited the activation of NF-κB, lessened the expression of iNOS,
*AChE↓, ICR mice 2.5 mg/kg Inhibited AchE activity
*H2S↑, SD rats 1, 10, 100 μM Upregulation of H2S,
Casp3↑, Anti-lung cancer A549 cells, Balb/c-nude mice 15, 20, 25 μM in vitro 15, 20, 25 mg/kg in vivo Activation of caspase-3 to motivate apoptosis and inactivation of NF-κB to inhibit inflammatory
Apoptosis↑,
NF-kB↓,
AMPK↑, A549 cells 10, 50, 100 μM Upregulation of AMPK signal pathway and HO-1 expression to suppressed the survival and proliferation of A549 cells
HO-1↑,
MAPK↑, A549 cells, H466 cells, C57BL/6J mice – Upregulated the expression of p38 MAPK, caspase 3, caspase 9, cleaved caspase 3, cleaved caspase 9 and Bax, downregulated the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1 and Bcl-2
cl‑Casp3↑,
cl‑Casp9↑,
BAX↑,
SOD?,
Catalase↓,
NRF2↓,
NQO1↓,
HO-1↓,
Bcl-2↓,
TumCCA↑, A549 cells 10, 20, 50, 100, 200, 400 μg/mL Inhibited the process of G1/S phase to inhibit proliferation
FOXO1↑, NCI-H1975 cells, PC-9 cells, Nude male mice 30, 60, 90, 120, 150 μM in vitro, 25 mg/kg in vivo Upregulation of FoxO1
TumAuto↑, A549 cells 0.5, 1, 2 mM Induced autophagy through inhibiting the Akt/mTOR/p70S6K signal pathway
Akt↓,
mTOR↓,
P70S6K↓,
BMP7/OP1↓, HepG2 cells 5, 10, 20, 40, 80 μM Inhibiting the BMP-7
*cardioP↑, Cardiovascular Protective Effect
*hepatoP↑, Hepatoprotective
*antiCG↑, The report indicates hyperoside possesses antithrombotic activities and offer bases for development of a novel anticoagulant
*AntiThr↑,
*Diar↓, Antidiarrheal Activity
*AntiFungal↑, Antifungal Activity
*CYP2D6↓, hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and might cause herb-drug interactions when co-administrated with CYP2D substrates.
*PDGFR-BB↓, In diabetic rats’ model, hyperoside inhibited the platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor-B receptor (PDGFR-β) ligand binding
*PDGFRB↓,
*toxicity↓, In research conducted in Wistar rats, the researchers demonstrated that in a long-term oral administration lasted for 6 months, hyperoside has a good safety. And the possible target organ of toxicity is kidney and the damage is reversible
*Half-Life↑, hyperoside also showed a long half-life for 4 hours and the safety experiments also proves that it has good safety.

7548-

HYP,

Mechanistic evaluation of hyperoside against non-small cell lung cancer: a combined approach of network pharmacology and in vitro experimental validation

in-vitro,

NSCLC,

A549

IC50 values for Hyp at 24, 48, and 72 h in this study were 149.41, 102.88, and 64.26 µM, respectively.

MMP9↓, Analysis of the PPI network revealed a key network module and five key targets: MMP9, CASP3, MAPK1, ESR1, and EGFR.
cl‑Casp3↑, Cleaved-Caspase-3 and Bax increased significantly (
MAPK↑,
EGFR↓,
TumCP↓, Hyp inhibited proliferation and induced apoptosis of A549 cells
p38↑, Hyp could activate the p38/MAPK and JNKinduced mitochondrial death pathway, remarkably accelerating the A549 cells apoptosis
Apoptosis↑,
BAX↑, Cleaved-Caspase-3 and Bax increased significantly (
ERK↓, Hyp inhibited the activities of EGFR and ERK1/2 and downregulated the expression of FOXO1.
FOXO1↓,

7554-

HYP,

Effect of hyperoside on the apoptosis of A549 human non‑small cell lung cancer cells and the underlying mechanism

in-vitro,

NSCLC,

A549

10, 50 and 100 µM

tumCV↓, HY significantly inhibited the viability of A549 cells in a time- and dose-dependent manner, and enhanced the percentage of apoptotic cells.
Apoptosis↑,
p‑MAPK↑, HY also significantly increased the protein phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK),
JNK↑,
MMP↓, disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis-inducing factor into the cytosol.
Cyt‑c↑,
Casp9↑, HY also activated the expression of caspase-9 and caspase-3.
Casp3↑,
AIF↑, HY induces the release of cytochrome c and AIF

7385-

IBC,

Fighting cancer by triggering non-canonical mitochondrial permeability transition-driven necrosis through reactive oxygen species induction

vitro+vivo,

Lung,

A549

in-vitro,

BC,

4T1

Apoptosis↑, Previous reports demonstrated that isobavachalcone (IBC), a natural chalcone, has anticancer effect by apoptosis induction
necrosis↑, Here, we found that IBC induced regulated necrosis in cancer cells
ROS↑, IBC triggered non-apoptotic cell death in lung and breast cancer cells mediated by reactive oxygen species (ROS)
mtDam↑, IBC caused mitochondrial injury and dysfunction as evidenced by mitochondrial Ca2+ overload, the opening of MPT pore, mitochondrial membrane potential collapse, and structural damages
Ca+2↑,
MPT↑,
MMP↓,
AntiCan↑, In addition, IBC showed an anticancer effect in a 4T1 breast cancer cell-derived allograft mouse model
*AntiBio↑, Isobavachalcone (IBC), a natural chalcone, has anticancer, antimicrobial, anti-inflammatory, antioxidative, and neuroprotective activities
*Inflam↓,
*antiOx↓,
*neuroP↑,
p‑Akt↓, IBC potentially inhibits Akt by reducing Akt phosphorylation in lung cancer cells
DHODH↓, in acute myeloid leukemia cells, IBC directly targets dihydroorotate dehydrogenase (DHODH) to induce apoptosis and differentiation . BC is a potent inhibitor of Akt and DHODH [24,25] and actively regulates MAPKs
Diff↑,
MAPK↑, robust MAPK activation by IBC

7758-

ISL,

Targeting the JAK/STAT pathway with isoliquiritigenin in ovarian cancer: molecular mechanisms and therapeutic implications

Review,

Ovarian,

JAK↓, ISL exerts significant anti-ovarian cancer effects through multitarget regulation of the JAK/STAT pathway.
STAT↓,
toxicity↓, With the advantages of low toxicity and multi-pathway modulation, ISL is a promising natural candidate for targeted therapy,
*antiOx↑, exhibits significant antioxidant capacity, effectively scavenging free radicals and reducing oxidative stress-induced cellular damage
*ROS↓,
*NRF2↑, By activating the Nrf2/ARE signaling pathway, ISL induces the expression of antioxidant enzymes such as HO-1 and NQO1, thereby enhancing cellular antioxidant defense systems
*ARE↑,
*HO-1↑,
*NQO1↑,
*Inflam↓, Regarding anti-inflammatory effects, ISL suppresses NF-κB and MAPK signaling pathways, reducing inflammatory factor production and alleviating inflammatory responses
*NF-kB↓,
*MAPK↓,
*SOD↑, it maintains intracellular antioxidant defense mechanisms, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity to mitigate oxidative stress-induced cellular damage
*Catalase↑,
*GPx↑,
*AntiViral↑, Its antiviral activity manifests as ISL’s ability to disrupt viral replication cycles, inhibit viral protein synthesis, and suppress multiple viruses.
*NADPH↑, ISL reduces ROS production by activating the Nrf2 pathway or upregulating NADPH oxidase expression and activity
ROS↓, In SK-MEL-28 melanoma cells, ROS inhibition suppressed p38α (Thr180/Tyr182) phosphorylation, blocked the p38-mTOR-STAT3 (Ser727) cascade. This leads to decreased STAT3 transcriptional activity, silencing downstream cyclin D1 and survivin expression,
p38↓,
mTOR↓,
STAT3↓,
cycD1/CCND1↓,
survivin↓,
p38↑, ISL inhibits autophagy flux in pancreatic cancer cells by activating the p38-MAPK signaling pathway,
MAPK↑,
mtDam↑, This mechanism disrupts cellular clearance of damaged mitochondria, triggers endoplasmic reticulum stress and oxidative stress, ultimately inducing apoptosis.
ER Stress↑,
ROS↑,
Apoptosis↑,
GLUT4↓, chemically synthesized derivative ISL-17 in MKN45 gastric cancer cells interferes with energy metabolism (Warburg effect) by inhibiting GLUT4-mediated glucose uptake, leading to decreased ATP levels and increased ROS accumulation.
ATP↓,
Glycolysis↓, This process triggers an energy crisis by blocking glycolysis and oxidative phosphorylation, further enhancing the cytotoxic effects of ROS and thereby inhibiting tumor growth
eff↑, Combining ISL with mTOR inhibitors significantly enhances growth inhibition of ovarian cancer cells by dual blockade of the PI3K/Akt/mTOR pathway

5118-

JG,

Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells

in-vitro,

HCC,

HepG2

m-ROS↑, JG-induced ROS production caused oxidative damage to mitochondria and DNA
DNAdam↑,
Apoptosis↑, JG kills HepG2 cells through the induction of apoptosis.
TumAuto↑, JG triggers autophagy, which contributes to JG-induced cell death.
p38↑, The autophagic cell death was dependent on ROS generation and the activation of p38 MAPK and JNK pathways.
MAPK↑,
JNK↑,
MMP↓, closely related with loss of mitochondrial membrane potential,
LC3II↑, increased expressions of LC3-II and Beclin-1
Beclin-1↑,

Showing Research Papers: 1 to 50 of 89
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 89

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiBio↑, 2, antiCG↑, 1, CYP2D6↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 13, ARE↑, 1, Catalase↑, 3, GPx↑, 2, GSH↑, 5, H2O2∅, 1, HDL↑, 1, HO-1↓, 1, HO-1↑, 1, Keap1↓, 1, lipid-P↓, 1, MDA↓, 3, NQO1↑, 1, NRF2↑, 6, Prx↑, 1, ROS↓, 6, SOD↑, 4, SOD1↑, 1, SOD2↑, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 2,

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 2, CREB↑, 1, glucose↑, 1, glucose↝, 1, GlucoseCon↑, 1, GLUT2↑, 1, H2S↑, 1, HMG-CoA↓, 1, NADPH↑, 1, PPARγ↓, 1,

Cell Death(tgid=5) ⓘ

Akt↑, 6, BAX↓, 1, Casp3?, 1, Casp3↓, 2, Casp9↓, 1, Fas↓, 1, HGF/c-Met↑, 1, iNOS↓, 1, MAPK↓, 2, MAPK↑, 7, p38↑, 1,

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1, ER Stress↓, 1, GRP78/BiP↑, 1, GRP94↑, 1, HSP90↑, 1,

DNA Damage & Repair(tgid=10) ⓘ

p16↓, 1, P53↑, 1, TP53↑, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↑, 5, p‑ERK↑, 1, Jun↓, 1, PDGFRB↓, 1, PI3K↑, 6, PTEN↓, 2,

Migration(tgid=13) ⓘ

AntiAg↑, 1, APP↓, 1, Ca+2↝, 1, MMP9↓, 2, PKA↑, 1, PKCδ↑, 2, TumCP↓, 1, VCAM-1↓, 3,

Angiogenesis & Vasculature(tgid=14) ⓘ

eNOS↑, 1, NO↓, 1, PDGFR-BB↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2, GLUT1↑, 1, GLUT4↑, 2,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1, ICAM-1↓, 1, IL1β↓, 3, IL6?, 1, IL6↓, 1, IL8↓, 1, Imm⇅, 1, Inflam↓, 12, NF-kB↓, 6, NF-kB↑, 1, TLR4↓, 2, TNF-α↓, 4,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1, ADAM10↑, 1, BDNF↑, 3, NGF↑, 1, p‑tau↓, 1, TrkB↑, 2,

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1, Aβ↓, 1, BACE/β-secretase↓, 1, IDE↑, 1, PP2A↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

BP↝, 1, IL6?, 1, IL6↓, 1, TP53↑, 1,

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 4, chemoP↑, 1, cognitive↑, 4, hepatoP↑, 4, memory↑, 2, neuroP↑, 9, RenoP↑, 1, toxicity↓, 3, toxicity↝, 2,

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1, AntiViral↑, 2, Diar↓, 1,
Total Targets: 120

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase

7 Allicin (mainly Garlic)
6 Thymoquinone
5 Magnetic Fields
5 Quercetin
4 Chrysin
3 Hyperoside
2 Alpha-Lipoic-Acid
2 Ashwagandha(Withaferin A)
2 Berberine
2 Betulinic acid
2 brusatol
2 Copper and Cu NanoParticles
2 Curcumin
2 Sulforaphane (mainly Broccoli)
2 Cynaropicrin
2 Fucoidan
2 Juglone
2 Oxygen, Hyperbaric
2 Piperlongumine
2 Resveratrol
1 Silver-NanoParticles
1 DTS(dibenzyl trisulphide) from Anamu
1 Bicarbonate(Sodium)
1 beta-glucans
1 Baicalin
1 Bacopa monnieri
1 Boswellia (frankincense)
1 Caffeic acid
1 Propolis -bee glue
1 Chlorogenic acid
1 Cisplatin
1 Dihydrocaffeic Acid
1 Emodin
1 Evodiamine
1 Fisetin
1 Formononetin
1 Ginseng
1 Honokiol
1 HydroxyTyrosol
1 Isobavachalcone
1 Isoliquiritigenin
1 Luteolin
1 Methylene blue
1 Photodynamic Therapy
1 Melatonin
1 Methyl salicylate / Sweet Birch oil
1 Magnesium
1 Methylglyoxal
1 Naringin
1 Phenethyl isothiocyanate
1 Propyl gallate
1 Piperine
1 Rutin
1 salinomycin
1 Oxaliplatin
1 Selenium
1 Aflavin-3,3′-digallate
1 Vitamin C (Ascorbic Acid)
1 Vitamin K2

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

MAPK Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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