CHOP Cancer Research Results

CHOP, GADD153: Click to Expand ⟱

Source:

Type: Protein

GADD153 and CHOP (C/EBP-homologous protein) refer to the same protein. GADD153 stands for "Growth Arrest and DNA Damage-inducible protein 153," while CHOP stands for "C/EBP Homologous Protein."
DDIT3 (DNA Damage Inducible Transcript 3), also known as CHOP (C/EBP Homologous Protein), is a transcription factor that plays a significant role in the cellular response to stress, particularly in the context of the unfolded protein response (UPR) and apoptosis.

CHOP is an important component of the endoplasmic reticulum (ER) stress response. Research has shown that knockdown of CHOP not only enhances tunicamycin-induced autophagy, but also significantly attenuates ER stress-induced apoptosis in human colon cancer cells.
GADD153, also known as CHOP (C/EBP homologous protein), is a transcription factor that plays a significant role in cellular stress responses, particularly in the context of the endoplasmic reticulum (ER) stress response. It is part of the unfolded protein response (UPR), which is activated when there is an accumulation of misfolded proteins in the ER.

Scientific Papers found: Click to Expand⟱

4561-

AgNPs,

VitC,

Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts

in-vitro,

CRC,

HCT116

in-vitro,

Nor,

HEK293

NRF2↑, Nanosilver increased Nrf2 protein expression and disrupted the cell cycle at the G1 and G2/M phases.
TumCCA↑, AgNPs interact with DNA to stop the cell cycle and lead to apoptosis
ROS↑, Nanosilver induced significant mitochondrial oxidative stress in HCT116, whereas it did not in the non-cancer HIEC-6 and nanosilver/sodium ascorbate co-treatment was preferentially lethal to HCT116 cells,
selectivity↑,
*AntiViral↑, AgNPs are effective antiviral agents against various viruses such as human immunodeficiency virus, hepatitis B virus, and monkey pox virus through interaction with surface glycoproteins on the virus
*toxicity↝, Citrate and PVP-coated AgNPs have been found to be less toxic than non-coated AgNPs
ETC↓, AgNPs affects mitochondrial function through the disruption of the electron transport chain2,24,26,33,39–41
MMP↓, Studies have shown that exposure to AgNPs resulted in a decrease of mitochondrial membrane potential (MMP) in various in vitro and in vivo experiments
DNAdam↑, AgNPs has also been shown to interact with and induce damage to DNA, DNA strand breaks, DNA damage
Apoptosis↑, apoptosis induced by AgNPs were through membrane lipid peroxidation, ROS, and oxidative stress
lipid-P↑,
other↝, Several studies have showed AgNPs interact with various proteins such as haemoglobin, serum albumin, metallothioneins, copper transporters, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), and bacterial proteins.
UPR↑, Studies have shown exposure to AgNPs induces activation of the UPR
*GRP78/BiP↑, AgNPs induced increased levels of GRP78, phosphorylated PERK, phosphorylated eIF2-α, and phosphorylated IRE1α, spliced XBP1, cleaved ATF-6, CHOP, JNK and caspase 12
*p‑PERK↑,
*cl‑eIF2α↑,
*CHOP↑,
*JNK↑,
Hif1a↓, One study showed AgNPs inhibits HIF-1 accumulation and suppresses expression of HIF-1 target genes in breast cancer cells (MCF-7) and also found the protein levels of HIF-1α and HIF-1β decreased
AntiCan↑, Many studies have shown that ascorbic acid, on its own, has anti-cancer effects
*toxicity↓, However, when the rats were treated with both ascorbic acid and AgNPs, a decrease in toxic effects was observed in non-cancer parotid glands in rats
eff↑, Studies have shown both AgNPs and ascorbic acid have greater effects and toxicity in cancer cells relative to non-cancer cells

5146-

AgNPs,

Silver Nanoparticle-Induced Autophagic-Lysosomal Disruption and NLRP3-Inflammasome Activation in HepG2 Cells Is Size-Dependent

in-vitro,

Liver,

HepG2

TumAuto↑, Overall, 10-nm AgNPs showed the highest cellular responses compared with 50- and 100-nm AgNPs . autophagy-lysosomal system
EPR↑, 10-nm AgNPs exhibited the highest uptake and accumulation.
LC3B↑, Subcytotoxic concentrations of AgNPs enhanced expression of LC3B, a pro-autophagic protein, and CHOP, an apoptosis inducing ER-stress protein, and activation of NLRP3-inflammasome (caspase-1, IL-1β).
CHOP↑,
ER Stress↑,
NLRP3↑,
Casp1↓,

5145-

AgNPs,

Silver nanoparticles induce irremediable endoplasmic reticulum stress leading to unfolded protein response dependent apoptosis in breast cancer cells

in-vitro,

BC,

MCF-7

in-vitro,

BC,

T47D

Bacteria↓, Nowadays, silver nanoparticles (AgNP) are widely used in the medical field mainly for their antibacterial properties
Apoptosis↑, AgNP of 2 (AgNP2) and 15 nm (AgNP15) induce apoptosis in human MCF-7 and T-47D breast cancer cells.
ER Stress↑, Treatment with AgNP2 and AgNP15 led to accumulation and aggregation of misfolded proteins causing an endoplasmic reticulum (ER) stress and activating the unfolded protein response (UPR).
UPR↑,
PERK↑, The three main ER sensors, PERK, IRE-1α and ATF-6, were rapidly activated in response to AgNP2 and AgNP15
IRE1↑,
ATF6↑,
ATF4↑, AgNP2 and AgNP15 induced upregulation of the transcription factors ATF-4 and GADD153/CHOP
CHOP↑,
Casp9↑, Moreover, the initiating caspase-9 and the effector caspase-7 were activated in response to these NPs.
Casp7↑,
Mcl-1↓, In contrast, a downregulation of Mcl-1 and xIAP protein expression as well as a processing of PARP were observed.
XIAP↓,
PARP↝,
selectivity↑, Of note, the non-cancerous MCF-10A cells were more resistant to both AgNP2 and AgNP15 when compared to MCF-7 and T-47D cell lines.

354-

AgNPs,

Silver nanoparticles induce SH-SY5Y cell apoptosis via endoplasmic reticulum- and mitochondrial pathways that lengthen endoplasmic reticulum-mitochondria contact sites and alter inositol-3-phosphate receptor function

in-vitro,

neuroblastoma,

SH-SY5Y

  Ca2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death.

TumCD↑, dose dependent manner
ER Stress↑,
GRP78/BiP↑,
p‑PERK↑, p-PERK
CHOP↑,
Ca+2↑, enhanced mitochondrial Ca2+ uptake
XBP-1↑,
p‑IRE1↑,

387-

AgNPs,

Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells

in-vitro,

Colon,

HT-29

33.45 μg/mL

Cyt‑c↑,
P53↑,
BAX↑,
Casp3↑,
Casp9↑,
Casp12↑,
Beclin-1↑,
CHOP↑,
LC3s↑, LC3-II
XBP-1↑,

2288-

AgNPs,

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Review,

Var,

*ROS↑, Several studies have reported that AgNPs induce genotoxicity and cytotoxicity in both cancer and normal cell lines
Akt↓, high ROS levels, and reduced Akt and ERK signaling.
ERK↓,
DNAdam↑, increased ROS production, leading to oxidative DNA damage and apoptosis
Ca+2↑, The damage caused to the cell membrane is due to intracellular calcium overload, and further causes ROS overproduction and mitochondrial membrane potential variation
ROS↑,
MMP↓,
Cyt‑c↑, AgNPs induce apoptosis through release of cytochrome c into the cytosol and translocation of Bax to the mitochondria, and also cause cell cycle arrest in the G1 and S phases
TumCCA↑,
DNAdam↑, main result of AgNP toxicity is direct and oxidative DNA damage, ultimately causing apoptosis
Apoptosis↑,
P53↑, AgNPs induce apoptosis in spermatogonial stem cells through increased levels of ROS; mitochondrial dysfunction; upregulation of p53 expression; pErk1/2;
p‑ERK↑,
ER Stress↑, endoplasmic reticulum (ER) stress-induced apoptosis caused by AgNPs has attracted much research interest
cl‑ATF6↑, cleavage of activating transcription factor 6 (ATF6), and upregulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153)
GRP78/BiP↑,
CHOP↑,
UPR↑, In order to protect the cells against nanoparticle-mediated toxicity, the ER rapidly responds with the unfolded protein response (UPR), an important cellular self-protection mechanism

264-

ALA,

α-Lipoic acid induces Endoplasmic Reticulum stress-mediated apoptosis in hepatoma cells

in-vitro,

HCC,

FaO

 500uM

ROS↑,
P53↑,
ER Stress↑,
UPR↑,
CHOP↑,
PDI↑,
GRP78/BiP↑,
GRP58↓,

1351-

And,

MEL,

Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids

in-vitro,

CRC,

T84

in-vitro,

CRC,

COLO205

in-vitro,

CRC,

HT-29

in-vitro,

CRC,

DLD1

eff↑, dual therapy significantly promotes CRC cell death
Ki-67↓,
Casp3↑,
ER Stress↑,
ROS↑,
BAX↑,
XBP-1↑,
CHOP↑, Apoptosis signaling molecules BAX, XBP-1, and CHOP were significantly increased
eff↑, combinatorial treatment increased reactive oxygen species (ROS) levels

2631-

Api,

Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells

in-vivo,

GC,

mice

in-vitro,

GC,

AGS

ER Stress↑, We further show that APG induces ER stress- and autophagy-related cell death through the inhibition of HIF-1α and Ezh2 under normoxia and hypoxia.
Hif1a↓, APG Inhibits HIF-1α and Induces Cell Death under Hypoxia in GC Cells
EZH2↓,
HDAC↓, Apigenin, a flavonoid found in traditional medicine, fruits, and vegetables and an HDAC inhibitor, is a powerful anti-cancer agent against various cancer cell lines.
TumAuto↑, APG Induces Autophagic Cell Death in GC Cells
p‑mTOR↓, APG decreased the phosphorylation of mTOR and increased the activation of AMPKα and ULK1
AMPKα↑,
GRP78/BiP↑, APG mediates the up-regulation of GRP78 through exosomes, and that this effect causes ER stress-induced cell death in APG-treated GC cells.
ROS↑, APG generates intracellular ROS release in colorectal cancer cells, and it causes various cell death types, including cell cycle arrest, chromatin condensation, MMP loss, intracellular Ca2+, annexin-v-positive cells, and ER stress-related cell death
MMP↓,
Ca+2↑, we found that APG exerts intracellular Ca2+ release in a dose- and time-dependent manner
ATF4↑, APG also increased ATF4 and CHOP in a time-dependent manner
CHOP↑,

2632-

Api,

Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress

in-vitro,

EC,

 20–60 μM

45.55 μM

TumCP↓, We found that API could inhibit the proliferation of Ishikawa cells at IC50 of 45.55 μM, arrest the cell cycle at G2/M phase, induce apoptosis by inhibiting Bcl-xl and increasing Bax, Bak and Caspases.
TumCCA↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
Bak↑,
Casp↑,
ER Stress↑, Further, API could induce apoptosis by activating the endoplasmic reticulum (ER) stress pathway by increasing the Ca2+, ATF4, and CHOP.
Ca+2↑, after API treatment for 48 h, the intracellular Ca2+ concentration increased in cells in a dose-dependent manner.
ATF4↑,
CHOP↑,
ROS↑, the level of intracellular ROS increased gradually with the increase of API concentration.
MMP↓, mitochondrial membrane potential of 30 μM, 50 μM, and 70 μM groups decreased by 2.19%, 11.32%, and 14.91%, respectively.
TumCMig↓, API inhibits the migration and invasion of Ishikawa cells and the migration and invasion related gene and protein.
TumCI↓,
eff↑, In our study, API restrained the viability of Ishikawa cells, and the inhibition effect of API on Ishikawa cells was better than that of 5-FU.
P53↑, API induces p53 tumor suppressor proteins at the translational level and the induces p21
P21↑,
Cyt‑c↑, After the mitochondria release the Cyto-c, the Caspase-9 is activated, resulting in increased activity of Caspases
Casp9↑, In our study, the expression levels of Bad, Bax, Cyto-c, Caspase-9 and Caspase-3 proteins were up-regulated,
Casp3↑,
Bcl-xL↓, while the expression level of Bcl-xl was down-regulated

2634-

Api,

Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells

in-vitro,

CRC,

HCT116

TumCG↓, Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase
TumCCA↑,
MMP↓, decreased mitochondrial membrane potential of the treated cells
ROS↑, Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells.
Ca+2↑,
ER Stress↑,
mtDam↑, together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.
CHOP↑,
DR5↑,
cl‑BID↑,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
Apoptosis↑,

3387-

ART/DHA,

Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment

Review,

Var,

BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
lipid-P↑, promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo.
Ferroptosis↑,
Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
GPx4↓, GPX4-dependent defense system is significantly inhibited
GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
PERK↑,
ATF4↑,
GRP78/BiP↑,
CHOP↑, which activates CHOP
ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
NRF2↑, ARTEs can activate the nuclear factor erythroid-derived 2-like 2 (Nrf2) -γ-glutamyl-peptide pathway in cancer cells, resulting in cancer cell ferroptosis resistance

5133-

ART/DHA,

Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells

in-vitro,

GBM,

U87MG

in-vitro,

GBM,

U251

AntiTum↑, (DHA) has been shown to exhibit anti-tumor activity in various cancer cells.
tumCV↓, Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay.
Apoptosis↓, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9.
MMP↓,
Cyt‑c↑,
Casp9↑,
CHOP↑, Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis
GRP78/BiP↑,
eIF2α↑,
Casp12↑,
ER Stress↑, DHA Induced Apoptosis through Mitochondria and Endoplasmic Reticulum (ER) Stress Pathways of Apoptosis in Human GBM Cells
TumAuto↑, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy.
ROS↑, Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy.

2572-

ART/DHA,

SRF,

Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax

in-vitro,

AML,

CHOP↑, Artemisinins increased CHOP, decreased MCL1,
Mcl-1↓,
ChemoSen↑, synergized with BCL2 inhibitors and SOR against human acute leukemia cells in vitro.
selectivity↑, The SAV combination potently inhibited leukemia cell growth but spared normal HSPCs

3156-

Ash,

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

Review,

Var,

MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
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↑,
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↓,
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↓,

3162-

Ash,

Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A

Review,

Var,

lipid-P↓, Oral cancer 20 mg/Kg ↓Lipid peroxidation : ↑SOD, glutathione peroxidase, p53, Bcl-2
SOD↑,
GPx↑,
P53↑,
Bcl-2↑,
E6↓, Cervival cancer 8mg/Kg ↓E6, E7: ↑p53, pRb, Cyclin B1, P34 Cdc2, p21, PCNA
E7↓,
pRB↑,
CycB/CCNB1↑,
CDC2↑,
P21↑,
PCNA↓,
ALDH1A1↓, Mammary cancer 0-1 mg/mouse (5-10) ↓Mammosphere number, ALDH1 activity. Vimentin, glycolysis
Vim↓,
Glycolysis↓,
cMyc↓, Mesotheliome cancer 5 mg/Kg ↓Proteasomal chymotrypsin, C-Myc : ↑ Bax, CARP-1
BAX↑,
NF-kB↓,
Casp3↑, caspase-3 activation
CHOP↑, WA is found to increase activation of Elk1 and CHOP (CCAAT-enhancer-binding protein homologous protein) by RSK, as well as up-regulation of DR5 by selectively suppressing pathway ERK
DR5↑,
ERK↓,
Wnt↓, WA inhibits Wnt/Î²-catenin pathway via suppression of AKT signalling, which inhibits cancer cell motility and sensitises for cell death
β-catenin/ZEB1↓,
Akt↓,
HSP90↓, WA-dependent inhibition of heat shock protein (HSP) chaperone functions. WA inhibits the activity of HSP90-mediated function

1373-

Ash,

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells

in-vitro,

Kidney,

Caki-1

ER Stress↑,
p‑eIF2α↑,
XBP-1↑,
GRP78/BiP↑,
CHOP↑,
eff↓, Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress.

1360-

Ash,

immuno,

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer

in-vitro,

Lung,

H1650

in-vitro,

Lung,

A549

in-vitro,

CRC,

HCT116

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

mice

PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

2001-

Ash,

Withania somnifera: from prevention to treatment of cancer

Review,

Var,

toxicity↓, Some sedation, ptosis and ataxia were observed in Sprague-Dawley rats 15–20 minutes of administering a herbal concoction that contained WS at a large dose of 1–2 g/kg body weight [36]
TumW↓, Induction of apoptosis by WA has been noted in some in vivo models where treatment with 4 mg/kg WA, i.p. 5 times for 2 weeks markedly reduced MDA-MB-231 tumor weights in nude mice as well as increased apoptosis compared to tumors in control mice [56
Dose?, 20 mg/kg, oral 3X/wk for 14 wk Hamster Head and Neck Example
eff↝, showed that this chemopreventive capacity was dependent on a circadian pattern where hamsters dosed with WA at 8 AM and 12 PM showed 100% protection from oral tumor formation while those treated at 12 AM showed 50% incidence in oral tumors
Ki-67↓, WA treatment resulted in retarded tumor growth; reduction in cell proliferation marker Ki-67, survivin, and XIAP,
survivin↓,
XIAP↓,
PERK↑, higher protein expression of pERK, pRSK, CHOP and DR-5 was also observed in the WA-treated group compared to control.
p‑RSK↑,
CHOP↑,
DR5↑,
Dose↝, Clinically diagnosed schizophrenia patients who had received antipsychotic medications for 6 months or more received either a capsule with 400 mg of WS extract (n=15), three times daily, for 1 month [80]
BG↓, Results after one month showed significant reduction in serum triglycerides and fasting blood glucose levels in the WS extract- treated group compared to the placebo
DNMTs↓, in MCF7 and MDA-MB-231 breast cancer cells WA treatment suppressed transcription of DNMT.

2479-

Ba,

Baicalein Overcomes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Resistance via Two Different Cell-Specific Pathways in Cancer Cells but not in Normal Cells

in-vitro,

HCC,

SW480

 40 μmol/L

in-vitro,

Pca,

PC3

12LOX↓, Baicalein is also known as a selective 12-lipoxygenase (12-LOX) inhibitor
DR5↑, Baicalein induces DR5 mRNA and protein expression in SW480 cells
CHOP↑, CHOP is increased by baicalein and responsible for DR5 up-regulation in SW480 cells
ROS↑, ROS are responsible for DR5 up-regulation in PC3 cells, but not in SW480 cells
*ROS∅,
selectivity↑, ROS are responsible for DR5 up-regulation in PC3 cells, but not in SW480 cells

2600-

Ba,

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

in-vitro,

HCC,

SMMC-7721 cell

19.89uM 48h

in-vitro,

HCC,

Bel-7402

ER Stress↑, Baicalein induced apoptosis via endoplasmic reticulum (ER) stress
Bcl-2↓, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK
Ca+2↑,
JNK↑,
CHOP↑, CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles.
Casp9↑, The results indicated that baicalein caused marked cleavage of caspase-9, caspase-3, and PARP dose- and time-dependently
Casp3↑,
PARP↑,
Apoptosis↑, these results demonstrated that baicalein promoted HCC cell death through inducing apoptosis.
UPR↑, Baicalein Induces ER Stress and Activates UPR Pathways

2295-

Ba,

5-FU,

Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway

in-vitro,

GC,

AGS

ChemoSen↑, baicalein increased the sensitivity of AGS cells to 5-FU treatment under hypoxia
HK2↓, hypoxia-enhanced glycolytic flux and expression of several critical glycolysis-associated enzymes (HK2, LDH-A and PDK1) in the AGS cells were suppressed by baicalein
LDHA↓,
PDK1↓,
Akt↓, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-1α (HIF-1α) expression in AGS cells
PTEN↑,
Hif1a↓,
Glycolysis↓, results together suggest that inhibition of glycolysis via regulation of the PTEN/Akt/HIF-1α signaling pathway may be one of the mechanisms whereby baicalein reverses 5-FU resistance in cancer cells under hypoxia.
ROS↑, Taniguchi et al found that baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in cancer cells through DR5 upregulation mediated by ROS induction and CHOP/GADD153 activation
CHOP↑,

2296-

Ba,

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms

Review,

Var,

CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

2681-

BBR,

PDT,

CHOP_in_human_malignant_melanoma_cells">Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells

in-vitro,

Melanoma,

Apoptosis↑, BBR-PDT induced apoptosis via up-regulating the expression of cleaved caspase-3 protein.
cl‑Casp3↑,
LC3s↑, LC3-related autophagy level was upregulated in MMCs with BBR-PDT.
ER Stress↑, BBR-PDT activated endoplasmic reticulum (ER) stress, involving a dramatic increase in reactive oxygen species (ROS).
ROS↑,
CHOP↑, knockdown of CHOP protein expression inhibited apoptosis, autophagy and ER stress levels caused by BBR-PDT, suggesting that CHOP protein may be related to apoptosis, autophagy and ER stress in MMCs with BBR-PDT

5634-

BCA,

Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1

in-vitro,

AML,

U937

in-vitro,

AML,

THP1

Apoptosis↑, Biochanin A induced dose-dependent apoptosis, as evidenced by caspase-7 activation and PARP1 cleavage.
Casp7↑,
PARP1↑,
Bcl-2↓, Biochanin A downregulated oncogenes such as RUNX1, BCL2, and MYC while upregulating CHOP (GADD153), CDKN1A (p21), and SQSTM1 (p62), contributing to apoptosis and cell cycle arrest across both cell lines.
Myc↓,
CHOP↑,
P21↑,
p62↑,
TumCCA↑,
TXNIP↑, In contrast, in U937 cells, Biochanin A upregulated TXNIP and downregulated CCND2, highlighting the involvement of oxidative stress and G1/S cell cycle arrest.
ROS↑,
*antiOx↑, Biochanin A exhibits a broad spectrum of biological activities, including antioxidant, anti-inflammatory, estrogenic, metabolic regulatory, neuroprotective, and anticancer effects [1].
*Inflam↓,
*neuroP↑,
AntiCan↑,
TumCP↓, The anticancer mechanisms of Biochanin A involve the inhibition of cell proliferation via the modulation of cyclins and cyclin-dependent kinases
angioG↓, inhibition of angiogenesis and metastasis through downregulation of VEGF and matrix metalloproteinases (MMPs), and activation of apoptosis
TumMeta↓,
VEGF↓,
MMPs↓,
tumCV↓, Biochanin A significantly inhibited cell viability at concentrations ≥100 μM in U937 cells and ≥50 μM in THP-1 cells
DNAdam↑, Biochanin A induces a DNA damage response
CHOP↑, In our study, we observed a significant induction of CHOP protein expression following treatment with Biochanin A at concentrations of 100 μM and 200 μM.
cMyc↓, Biochanin A inhibited c-Myc protein expression in U937 and THP-1 cells
BioAv↓, Biochanin A remains limited due to its poor aqueous solubility and rapid systemic clearance, which render the 100–200 μM concentrations used in this study difficult to achieve in vivo
Half-Life↓,
BioAv↑, PEG-NLC formulations have been shown to significantly increase the plasma half-life and bioavailability of flavonoids

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↑,
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.

2729-

BetA,

Betulinic acid in the treatment of tumour diseases: Application and research progress

Review,

Var,

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

744-

Bor,

Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5

in-vitro,

HCC,

HepG2

22.6 mM

in-vitro,

Nor,

HL7702

40.8 mM

TumCCA↑, cell cycle arrest in the G1/G0 phase
SLC12A5↓,
ATF6↑,
CHOP↑,
GRP78/BiP↑,
Casp3↑,
ER Stress↝,
*toxicity↓, HL‐7702 cells(normal) treated with 22.6 and 45.7 mM borax for 24 h showed no notable abnormalities in cellular size and cytoplasmic volume compared to the control group
*eff↓, tumour blood vessels absorb much higher levels of boric acid than normal liver tissues

2776-

Bos,

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

Review,

Var,

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

5674-

BTZ,

Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic, anti-tumor effects

in-vivo,

GBM,

in-vivo,

HNSCC,

ER Stress↑, Bortezomib treatment induced ER stress, evident by strong induction of Grp78, CHOP, PERK and IRE1α
GRP78/BiP↑,
CHOP↑,
PERK↑,
IRE1↑,
UPR↑, and the UPR (induction of hsp40, 70 and 90)
HSP70/HSPA5↑,
HSP90↑,
eff↑, combination of bortezomib and 34.5ENVE significantly enhanced anti-tumor efficacy in multiple different tumor models in vivo.

3032-

CA,

Carnosic Acid Induces Apoptosis Through Reactive Oxygen Species-mediated Endoplasmic Reticulum Stress Induction in Human Renal Carcinoma Caki Cells

in-vitro,

Kidney,

Caki-1

cl‑PARP↑, Carnosic acid induced sub-diploid DNA content, sub-G1, population and poly (ADP-ribose) polymerase (PARP) cleavage and activated caspase-3.
ROS↑, Carnosic acid promoted intracellular ROS production,
ER Stress↑, carnosic acid also induced expression of ER stress marker proteins, including activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP), in a dose- and time-dependent manner.
ATF4↑,
CHOP↑,
selectivity↑, Carnosic acid induced apoptosis in other cancer cells, but not normal cells

5849-

CAP,

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Review,

Var,

TRPV1↑, TRPV1 belongs to the transient receptor potential channel vanilloid subfamily and is also known as the capsaicin receptor and vanilloid receptor 1 (VR1).
Ca+2↑, The activation of TRPV1 induces the cellular influx of Ca2+ and Na+ ions 17-19, and the excess intracellular Ca2+ and Na+ leads to cell death 20.
TumCD↑,
TumCCA↑, Induced cell cycle arrest in G0/G1 phase and apoptosis by activating p53 to upregulate Fas/CD95 in TRPV1-overexpressing cells
Apoptosis↑,
P53↑,
Fas↑,
PI3K↑, Activated PI3K and p44/42 MAPK pathways to suppress ceramide production and increased androgen receptor expression
AR↑,
STAT3↓, attenuating STAT3 phosphorylation
ROS↑, Induced apoptosis by producing ROS originating from the mitochondria
MMP↓, Disrupted mitochondrial membrane potential and suppressed ATP synthesis to induce apoptosis
ATP↓,
CHOP↑, Stimulated ROS generation, increased CHOP expression level, and promoted apoptosis
TumCMig↓, As TRPV1 serves as the main Ca2+-influx channel, it is reasonable to suggest that TRPV1 could act as an enhancer or inhibitor of migration and invasion in a tissue- or cell-specific manner.
Twist↓, Capsaicin downregulated Tiwst1, Snail1, MMP2, and MMP9 and upregulated E-cadherin
Snail↓,
MMP2↓,
MMP9↓,
E-cadherin↑,

5818-

CBD,

Cannabidiol's cytotoxicity in pancreatic cancer is induced via an upregulation of ceramide synthase 1 and ER stress

in-vivo,

PC,

PANC1

GRP78/BiP↑, Upon CBD treatment, CerS1 was upregulated and downstream this led to the GRP78/ATF4/CHOP arm of the unfolded protein response (UPR) pathway being activated.
ATF4↑,
CHOP↑,
UPR↑,
TumCG↓, Cannabidiol reduces pancreatic cancer growth in a dose and time dependent manner
ER Stress↑, activation of GRP78, ATF4 arm of the UPR pathway further resulting in elevated CHOP expression which induces ER stress leading to apoptosis
eff↓, Additionally, drug-drug interactions are a problem with CBD intake as it involves metabolism by a competitive inhibitor of CYP450 enzymes

5948-

Cela,

Recent Trends in anti-tumor mechanisms and molecular targets of celastrol

TumCP↓, mechanism of action of celastrol in terms of inhibition of cell proliferation and regulation of the cell cycle, regulation of apoptosis and autophagy, inhibition of cell invasion and metastasis, anti-inflammation, regulation of immunotherapy, and an
TumCCA↑,
Apoptosis↑,
TumAuto↑,
TumCI↓,
TumMeta↓,
Imm↝,
angioG↓,
Cyt‑c↑, release of cytochrome c (CytC)
ROS↑, increasing ROS levels, and activating the mitochondrial apoptosis pathway
BAX↑, upregulating the expression of CytC and the pro-apoptotic protein Bax, activating caspase-3 and caspase-9, and leading to the cleavage of PARP
Casp3↑,
Casp9↑,
cl‑PARP↑,
PrxII↓, binds to peroxiredoxin-2 (Prdx2) and inhibits its enzyme activity,
ER Stress↑, resulting in ROS-dependent endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells
mtDam↑,
CHOP↑, celastrol upregulates the expression of CHOP, Bip, XBP1s, and IRE1 proteins,
Inflam↓, Anti-inflammatory properties of celastrol
NF-kB↓, Celastrol additionally obstructed NF-κB and its downstream gene products, such as CXCR4 and MMP9, and reduced serum IL-6 and TNF-α levels to inhibit cell invasion and migration in vivo
CXCR4↓,
MMP9↓,
IL6↓,
TNF-α↓,
HSP90↓, accumulation may be due to the inhibition of HSP90 and the stress response
neuroP↑, Our mass spectrometry research also showed that celastrol directly binds to HSP90 and HSP70, exerting antitumor and neuroprotective effects
STAT3↓, Celastrol exerts anti-tumor activity by inhibiting STAT3
Prx↓, celastrol binds directly to Prdx1, Prdx2, Prdx4, and Prdx6 via active cysteine sites, inhibiting their antioxidant activity without affecting protein expression
HO-1↑, Celastrol also targeted heme oxygenase-1 (HO-1), increasing its expression in activated hematopoietic stem cells
eff↑, Research has indicated that celastrol, combined with 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), inhibits the toxic stress response of HSP90-targeted proteins, reduces the sensitization of human glioblastomas to celastrol treatment, an
eff↑, celastrol, when combined with EGFR tyrosine kinase inhibitors (EGFR-TKIs), effectively inhibits the growth and invasion of T790M mutant human lung cancer H1975
BioAv↑, nano-delivery systems present a novel pathway for the development and clinical application of celastrol, potentially overcoming existing limitations and maximizing its therapeutic potential.
toxicity↑, several significant challenges, including its pronounced hepatic and renal toxicity and potential for causing immunosuppression
CardioT↑, celastrol, which includes hepatotoxicity, cardiotoxicity, infertility toxicity, hematopoietic system toxicity and nephrotoxicity.
hepatoP↓,

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↑, ↑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↓, ↓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↓,

1572-

Cu,

Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy

Review,

NA,

eff↑, generate a large number of reactive oxygen species (ROS) when exposed to light, which could be adopted for photodynamic therapy.
Fenton↑, Cu2+ is vulnerable to the reduction to Cu+, allowing Cu to drive the Fenton reaction and produce hydroxyl radicals (·OH).
ROS↑, increasing Cu ions in cancer tissue makes an antitumor impact that mainly involves OS by triggering the Fenton reaction, which can produce ROS
eff↑, compared with other metals (iron, chromium, cobalt and nickel), the Cu-based Fenton reaction can react in wider pH range
mtDam↑, Excessive Cu can induce the toxic level of ROS that may aggravate the mitochondrial ROS, causing mitochondrial damage
BAX↑, Cu-induced ROS increased Bax (pro-apoptotic protein), while Bcl2 (anti-apoptotic protein) was decreased
Bcl-2↓,
MMP↓,
Cyt‑c↑, releasing CytC that activated Caspase3
Casp3↑,
ER Stress↑, Nano-CuO) triggers OS by ROS, thus stimulating endoplasmic reticulum (ER)-stress
CHOP↑, which thereby enhanced the expression of CHOP
Apoptosis↑, and CHOP-induced apoptosis
selectivity↑, In fact, autophagy induced by copper can either protect cells from death or contribute to cell death, depending on autophagic flux, which is associated with the concentration of copper.
eff↑, combining artemisinin (ART) and copper peroxide nanodots to enhance autophagy and ferroptosis that produced highly cancer toxic reaction
Pyro↑, Copper-Based Pyroptosis
Paraptosis↑, Copper-Based Paraptosis
Cupro↑, Copper-Based Cuproptosis
ChemoSen↑, studies suggested that Cu-MOFs might be a robust nanoplatform for enhancing chemotherapy activity of Cu-organic compounds.
eff↑, CuS NPs had the ability to directly target cancer cells and then induce in nucleus by modification of RGD and TAT peptides, thus heating cancer cell to exhaustive apoptosis through 980 nm NIR irradiation

872-

CUR,

RES,

New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects

in-vitro,

BC,

TUBO

15uM, 15uM

in-vitro,

BC,

SALTO

TumCP↓,
tumCV↓,
p62↓, reduced by Cur
p62↑, accumulated by Res
TumAuto↑, Cur only
TumAuto↓, Res only
ROS↑, increased ROS with Res
ROS↓, decreased ROS with Cur or combination
CHOP↑, strongly upregulated by the curcumin/resveratrol combination

143-

CUR,

Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

ER Stress↑, curcumin treatment upregulated the ER stress markers CHOP and Bip/GRP78 and the autophagic marker LC3-II.
CHOP↑,
GRP78/BiP↑,
ROS↑, curcumin induced ER stress by triggering ROS generation
LC3II↑,
eff↓, treating cells with the antioxidant NAC alleviated curcumin-mediated ER stress and vacuolation-mediated death.
tumCV↓, Curcumin treatment results in reduced cell viability and altered morphology of prostate cancer cells

118-

CUR,

Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

in-vitro,

Pca,

PC3

 2.2 μM

 for WZ35 analog. For Curcumin it is 20.9μM

in-vitro,

Pca,

DU145

ROS↑, WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells.
Bcl-2↓,
PARP↑,
cDC2↓, decreased expression of CDC2, cyclinB1, and MDM2
CycB/CCNB1↓,
MDM2↓,
eff↓, Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis,
eIF2α↑, WZ35 treatment also induced a constant increase in the level of phosphorylated eIF2α 3 to 12 h after WZ35 treatment
ATF4↑, ATF4 expression also increased in a similar manner with p-eIF2α
CHOP↑, CHOP protein expression apparently increased 9-24 h after WZ35 treatment and peaked at 12 h
ER Stress↑, results suggest that WZ35 can induce ER stress in prostate cancer cells
TumCCA↑, WZ35 induced cell cycle arrest in G2/M phase in PC-3 cells

462-

CUR,

Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress

in-vitro,

Pca,

PC3

10, 20 and 30 μM, 8, 12 and 24 h

Bcl-2↓,
MMP↓,
cl‑Casp3↑,
BAX↑,
BIM↑,
p‑PARP↑,
PUMA↑,
p‑P53↑,
ROS↑,
p‑ERK↑,
p‑eIF2α↑,
CHOP↑,
ATF4↑,

414-

CUR,

Transcriptome Investigation and In Vitro Verification of Curcumin-Induced HO-1 as a Feature of Ferroptosis in Breast Cancer Cells

in-vitro,

BC,

MCF-7

114 μM

in-vitro,

BC,

MDA-MB-231

Ferroptosis↑,
Iron↑,
ROS↑,
lipid-P↑,
MDA↑,
GSH↓,
HO-1↑, Curcumin upregulates a variety of ferroptosis target genes related to redox regulation, especially heme oxygenase-1 (HO-1).
NRF2↑,
GPx↓,
ROS↑,
Iron↑, curcumin caused marked accumulation of intracellular iron
GPx4↓,
HSP70/HSPA5↑,
ATFs↑, ATF4
CHOP↑, DDIT3
MDA↑,
FTL↑, Curcumin upregulated FTL (encoding ferritin light chain), FTH1
FTH1↑,
BACH1↑,
REL↑, v-rel reticuloendotheliosis viral oncogene homolog A
USF1↑,
NFE2L2↑,

2821-

CUR,

Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)

Review,

Var,

*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,

1621-

EA,

The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art

Review,

Var,

AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

3203-

EGCG,

(-)- Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress

NA,

MM,

ROS↑, We have previously shown that (-)-epigallocatechin-3-gallate (EGCG) enhances ROS production and alters Ca2+ homeostasis in cell lines deriving from therapy-recalcitrant malignant mesothelioma (MMe).
Ca+2↝,
GRP78/BiP↑, Exposure to EGCG further increased GRP78 in the ER, and induced ATF4, spliced XBP1, CHOP, and EDEM expressions, combined with a reduction of cell surface GRP78 and a rise in caspase 3 and 8 activities.
ATF4↑,
XBP-1↑,
CHOP↑,
Casp3↑,
Casp8↑,
*GRP78/BiP↓, n non-cancer mouse retinal pigment epithelial cells,EGCG has been found to downregulate GRP78 and UPR signaling (Karthikeyan et al., 2017).
*UPR↓,
UPR↑, However, if ER homeostasiscannot be re-established, the UPR switches its signaling toward irreversible ER stress with the activation of apoptosis (

3205-

EGCG,

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas

Review,

Var,

Review,

AD,

Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

3460-

EP,

Picosecond pulsed electric fields induce apoptosis in HeLa cells via the endoplasmic reticulum stress and caspase-dependent signaling pathways

in-vitro,

Cerv,

HeLa

tumCV↓, psPEF displayed strong growth inhibitory effects on HeLa cells.
Apoptosis↑, psPEF led to marked cell apoptosis and cell cycle arrest at the G2/M phase.
TumCCA↑,
GRP78/BiP↑, psPEF affected the phosphorylation levels of endoplasmic reticulum sensors and upregulated the expression of glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and CCAAT enhancer-binding protein (C/EBP) homologous protein (CH
GRP94↑,
CEBPA↑,
CHOP↑,
Ca+2↑, These changes were accompanied by the elevation of intracellular Ca2+ concentrations
Casp12↑, activation of caspase-12, -9 and -3, led to the release of cytochrome c, as well as the upregulation of Bax and the downregulation of Bcl-2, as observed in the HeLa cells.
Casp9↑,
Casp3↑,
Cyt‑c↑,
BAX↑,
Bcl-2↓,
ER Stress↑, at least partially, via the endoplasmic reticulum stress and caspase-dependent signaling pathways.
MMP↓, which subsequently leads to mitochon- drial depolarization and initiates a cell death cascade

2496-

Fenb,

Impairment of the Ubiquitin-Proteasome Pathway by Methyl N-(6-Phenylsulfanyl-1H-benzimidazol-2-yl)carbamate Leads to a Potent Cytotoxic Effect in Tumor Cells

in-vitro,

NSCLC,

A549

1.6 μm

in-vitro,

NSCLC,

H460

1.2 uM

TumCG↓, We report that fenbendazole (FZ) (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate) exhibits a potent growth-inhibitory activity against cancer cell lines but not normal cells.
selectivity↑, but not normal cells
P53↑, A number of apoptosis regulatory proteins that are normally degraded by the ubiquitin-proteasome pathway like cyclins, p53, and IκBα were found to be accumulated in FZ-treated cells.
IKKα↑,
ER Stress↑, FZ induced distinct ER stress-associated genes like GRP78, GADD153, ATF3, IRE1α, and NOXA in these cells.
GRP78/BiP↑,
CHOP↑,
ATF3↑,
IRE1↑,
NOXA↑,
ROS↑, fenbendazole induced endoplasmic reticulum stress, reactive oxygen species production, decreased mitochondrial membrane potential, and cytochrome c release that eventually led to cancer cell death.
MMP↓,
Cyt‑c↑,
selectivity↑, treatment of human lung cancer cell lines with fenbendazole (FZ)3 induces apoptotic cell death, whereas primary normal cells in culture remain widely unaffected.
eff↝, The growth-inhibitory action of FZ in H460 and A549 cells was also compared with the Food and Drug Administration-approved proteasomal inhibitor bortezomib, and the results showed that the activities of both of the compounds were comparable

2855-

FIS,

Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

in-vitro,

RCC,

Caki-1

TumCCA↑, Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation.
cl‑PARP↑,
Apoptosis↑,
Casp↑,
P53↑, fisetin induced p53 protein expression
DR5↑, fisetin-induced DR5 expression.
CHOP↑, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis.
ROS↑,
ER Stress↑, Fisetin induced expression of ER stress-related proteins, including CHOP and activating ATF4
ATF4↑,
XBP-1↑, fisetin also increased the spliced form of the X-box binding protein (XBP)-1 mRNA
eff∅, In our study, NAC did not enhance fisetin-induced apoptosis, and the ROS scavenger, GEE, also had no effect on apoptosi

2857-

FIS,

A review on the chemotherapeutic potential of fisetin: In vitro evidences

Review,

Var,

COX2↓, fisetin altered the expression of cyclooxygenase 2 (COX2) thereby suppressed the secretion of prostaglandin E2 ultimately resulting in the inhibition of epidermal growth factor receptor (EGFR) and NF-ÎºB in human colon cancer cells HT29
PGE2↓,
EGFR↓,
Wnt↓, fisetin treatment inhibited the stimulation of Wnt signaling pathway via downregulating the expression of Î²-catenin and Tcell factor (TCF) 4
β-catenin/ZEB1↓,
TCF↑,
Apoptosis↑, fisetin triggers apoptosis in U266 cells through multiple pathways: enhancing the activation of caspase-3 and PARP cleavage, decreasing the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1 L ),
Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Mcl-1↓,
BAX↑, ncreasing the expression of pro-apoptotic proteins (Bax, Bim, and Bad)
BIM↑,
BAD↑,
Akt↓, decreasing the phosphorylation of AKT and mTOR and elevating the expression of acetyl CoA carboxylase (ACC
mTOR↓,
ACC↑,
Cyt‑c↑, release the cytochrome c and Smac/Diablo into the cytosol
Diablo↑,
cl‑Casp8↑, fisetin exhibited an increased level of cleaved caspase-8, Fas/Fas ligand, death receptor 5/TRAIL, and p53 levels in HCT-116 cells
Fas↑,
DR5↑,
TRAIL↑,
Securin↓, Securin gets degraded on exposure to fisetin in colon cancer cells.
CDC2↓, fisetin decreased the expression of cell division cycle proteins (CDC2 and CDC25C)
CDC25↓,
HSP70/HSPA5↓, Fisetin induced apoptosis as a result of the downregulation of HSP70 and BAG3 and the inhibition of Bcl-2, Bcl-x L and Mcl-1. T
CDK2↓, AGS 0, 25, 50, 75 μM – 24 and 48 h ↓CDK2, ↓CDK4, ↓cyclin D1, ↑casapse-3 cleavage
CDK4↓,
cycD1/CCND1↓,
MMP2↓, A549 0, 1, 5, 10 μM- 24 and 48 hr: ↓MMP-2, ↓u-PA, ↓NF- κB, ↓c-Fos, ↓c-Jun
uPA↓,
NF-kB↓,
cFos↓,
cJun↓,
MEK↓, ↓ MEK1/2 and ERK1/2 phosphorylation, ↓N-cadherin, ↓vimentin, ↓snail, ↓fibronectin, ↑E-cadherin, ↑desmoglein
p‑ERK↓,
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↓,
NF-kB↑, increased expression of NF-κB p65 leading to apoptosis was due to ROS generation on exposure to fisetin
ROS↑,
DNAdam↑, increased ROS triggered cell death through PARP cleavage, DNA damage and mitochondrial membrane depolarization.
MMP↓,
CHOP↑, Though fisetin upregulated CHOP expression and increased the production of ROS, these events fail to induce apoptosis in Caki cells.
eff↑, 50 μM fisetin + 1 mM melatonin Sk-mel-28 Enhances anti-tumour activity [54] 20 μM fisetin + 1 mM melatonin MeWo Enhances anti-tumour activity [54] 10 μM fisetin + 0.1 μM melatonin A549 Induces autophagic cell death
ChemoSen↑, 20 μM fisetin + 5 μM sorafenib A375, SK-MEL-28 Suppresses invasion and metastasis [44] 40 μM fisetin + 10 μM cisplatin A549, A549-CR Enhances apoptosis

Showing Research Papers: 1 to 50 of 104
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 104

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 321

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 5, Catalase↑, 2, GPx↑, 1, GSH↑, 2, HDL↑, 1, HO-1↓, 1, Keap1↓, 1, MDA↓, 1, MPO↓, 1, NRF2↑, 3, Prx↑, 1, ROS↓, 3, ROS↑, 1, ROS∅, 1, SOD↑, 2, SOD1↑, 1, SOD2↑, 1,

Core Metabolism/Glycolysis ⓘ

glucose↓, 1, glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 1, LDL↓, 1,

Cell Death ⓘ

BAX↓, 1, Casp3?, 1, Casp3↓, 1, Casp9↓, 1, Cyt‑c↓, 1, Fas↓, 1, HGF/c-Met↑, 1, iNOS↓, 2, JNK↑, 1, p‑JNK↓, 1, MAPK↓, 1, p38↓, 1,

Protein Folding & ER Stress ⓘ

CHOP↑, 2, cl‑eIF2α↑, 1, GRP78/BiP↓, 1, GRP78/BiP↑, 2, GRP94↑, 1, p‑PERK↑, 1, UPR↓, 1,

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↑, 1,

Migration ⓘ

5LO↓, 1, Ca+2?, 1, MMP3↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1, NO↑, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 2, IL1β↓, 2, IL6↓, 1, Inflam↓, 5, NF-kB↓, 2, PGE2↓, 1, PGE2↑, 1, Th1 response↓, 1, Th2↑, 2, TLR4↓, 2, TNF-α↓, 2,

Protein Aggregation ⓘ

AGEs↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↑, 1, BioAv↝, 1, eff↓, 1,

Clinical Biomarkers ⓘ

IL6↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 3, RenoP↑, 1, toxicity↓, 5, toxicity↝, 1,

Infection & Microbiome ⓘ

AntiViral↑, 1,
Total Targets: 72

Scientific Paper Hit Count for: CHOP, GADD153

7 Curcumin
7 Quercetin
6 Silver-NanoParticles
6 Ashwagandha(Withaferin A)
5 Fisetin
5 Piperlongumine
4 Baicalein
4 Resveratrol
4 Phenylbutyrate
4 Shikonin
3 Apigenin (mainly Parsley)
3 Artemisinin
3 Luteolin
3 salinomycin
2 Vitamin C (Ascorbic Acid)
2 Betulinic acid
2 EGCG (Epigallocatechin Gallate)
2 Garcinol
2 temozolomide
2 Honokiol
2 HydroxyTyrosol
2 Rosmarinic acid
1 Alpha-Lipoic-Acid
1 Andrographis
1 Melatonin
1 Sorafenib (brand name Nexavar)
1 immunotherapy
1 5-fluorouracil
1 Berberine
1 Photodynamic Therapy
1 Biochanin A
1 Boron
1 Boswellia (frankincense)
1 Bortezomib
1 Carnosic acid
1 Capsaicin
1 Cannabidiol
1 Celastrol
1 Chlorogenic acid
1 Copper and Cu NanoParticles
1 Ellagic acid
1 Electrical Pulses
1 Fenbendazole
1 Gambogic Acid
1 γ-linolenic acid (Borage Oil)
1 Graviola
1 hydroxychloroquine
1 Magnetic Fields
1 Naringin
1 nelfinavir/Viracept
1 Docetaxel
1 Oleuropein
1 Phenethyl isothiocyanate
1 Pterostilbene
1 Paclitaxel
1 Scoulerine
1 Selenium NanoParticles
1 Sulforaphane (mainly Broccoli)
1 Thymoquinone

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

CHOP Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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