UPR Cancer Research Results

UPR, Unfolded Protein Response: Click to Expand ⟱

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Type:

Cellular stress response related to the endoplasmic reticulum (ER) stress, which involves protein folding, quality control, and signaling pathways. The unfolded protein response (UPR) is the cells' way of maintaining the balance of protein folding in the endoplasmic reticulum. (UPR) is triggered by the presence of misfolded proteins in the endoplasmic reticulum.
The UPR is a cellular stress response activated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER).
- It is primarily mediated by three ER-resident sensors: IRE1α, PERK, and ATF6.

Cancer cells often experience high levels of protein synthesis, hypoxia, nutrient deprivation, and oxidative stress, all of which can activate the UPR.
– Numerous studies have reported that key UPR components (e.g., GRP78/BiP, IRE1α, PERK, CHOP) are overexpressed in various malignancies such as breast, pancreatic, lung, and prostate cancers.

Unfolded Protein Response is typically upregulated in cancers and is associated with poorer prognosis due to its role in promoting cell survival, adaptation to stress, and therapeutic resistance. Although the UPR harbors the potential for tumor-suppressive (apoptotic) effects under severe stress conditions, its predominant activation in tumors supports an adaptive, protumorigenic state that facilitates cancer progression. Targeting UPR components and modulating this balance remain promising therapeutic strategies.

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

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.

374-

AgNPs,

Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

 6, 9, or 12 mg total silver/kg

 mice

ER Stress↑,
DNAdam↑,
ROS↑,
Apoptosis↑,
GSH/GSSG↓, MDA‐MB‐231
NADPH/NADP+↓, MDA‐MB‐231
TumCG↓,
UPR↑, initiating UPR

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

2646-

AL,

Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress

in-vitro,

Pca,

DU145

in-vitro,

Melanoma,

RPMI-8226

AntiCan↑, simple homemade ethanol-based garlic extract (GE). We show that GE inhibits growth of several different cancer cells in vitro
eff↓, These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile.
ChemoSen↑, We found that GE enhanced the activities of chemotherapeutics
ER Stress↑, Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER) stress.
tumCV↓, homemade GE was found to reduce the viability of the two multiple myeloma (MM) cell lines, RPMI-8226 and JJN3, as well as the prostate cancer cell line DU145 in a dose-dependent manner,
DNAdam↑, GE alone slightly increased the percentage of tail DNA (% Tail) (representing cumulative levels of abasic sites, as well as single- and double-strand DNA breaks) measured at day one, compared to untreated cells
GSH∅, We could not detect any changes in cellular GSH levels after treatments with GE
HSP70/HSPA5↓, ; however, in support of increased ER stress after GE treatment, we detected an increased pulldown of HSPA5 (BIP), a member of the Hsp70 family
UPR↑, s leading to the accumulation of unfolded proteins in the ER (also known as GRP78)
β-catenin/ZEB1↓, we also found a reduction in the β-catenin leve
ROS↑, In further support for increased ER stress induced by GE, which will lead to elevated ROS-levels and oxidative stress
HO-2↑, we found a significant increase in proteins activated by and important for regulating cellular ROS levels, e.g., OXR1, Txnl1, Hmox2, and Sirt1
SIRT1↑,
GlucoseCon∅, glucose consumption, as well as lactate secretion, were not changed.
lactateProd∅,
chemoP↑, Garlic is reported to reduce cisplatin-induced nephrotoxicity and oxidative stress

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↓,

2633-

Api,

Apigenin induces ROS-dependent apoptosis and ER stress in human endometriosis cells

in-vitro,

EC,

TumCP↓, Apigenin reduced proliferation and induced cell cycle arrest and apoptosis in the both endometriosis cell lines
TumCCA↑,
MMP↓, In addition, it disrupted mitochondrial membrane potential (MMP) which was accompanied by an increase in concentration of calcium ions in the cytosol and in pro-apoptotic proteins including Bax and cytochrome c in the VK2/E6E7 and End1/E6E7 cells
Ca+2↑,
BAX↑,
Cyt‑c↑,
ROS↑, Moreover, apigenin treated cells accumulated excessive reactive oxygen species (ROS), and experienced lipid peroxidation and endoplasmic reticulum (ER) stress with activation of the unfolded protein response (UPR) regulatory proteins.
lipid-P↑,
ER Stress↑,
UPR↑,
p‑ERK↓, Apigenin inhibited the phosphorylation of ERK1/2
ERK↓, Similar to previous studies, apigenin-induced apoptosis was also mediated by inactivation of ERK1/2 and JNK proteins and regulation of AKT protein in human endometriosis cells.
JNK↑,

3384-

ART/DHA,

Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response‑induced upregulation of CHAC1 expression

in-vitro,

Liver,

Hep3B

29.4±1.7 µM

in-vitro,

Liver,

HUH7

32.1±4.5 µM

in-vitro,

Liver,

HepG2

40.2±2.1 µM

Ferroptosis↑, DHA displayed classic features of ferroptosis, such as increased lipid reactive oxygen species
ROS↑,
GSH↓, decreased activity or expression of glutathione (GSH), glutathione peroxidase 4, solute carrier family (SLC) 7 member 11 and SLC family 3 member 2.
UPR↑, DHA activated all three branches of the UPR
GPx4↓, GSH depletion leads to the suppression of glutathione peroxidase (GPX)4, a key glutathione peroxidase known to catalyze the reduction of lipid ROS
PERK↑, DHA was found to activate PERK/eIF2α/ATF4
eIF2α↑,
ATF4↑,

3157-

Ash,

Withaferin A and Ovarian Cancer Antagonistically Regulate Skeletal Muscle Mass

in-vivo,

Ovarian,

A2780S

mouse

*cachexia↑, suggesting that it could be an anti-cachectic agent in the settings of ovarian cancer.
*UPR↑, WFA treatment and our xenograft model differentially regulate the UPR pathways in skeletal muscle
Strength↑, promisingly, WFA treatment led to significant improvements in muscle grip strength

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

5542-

BBM,

Pharmacological profiling of a berbamine derivative for lymphoma treatment

vitro+vivo,

lymphoma,

CaMKII ↓, PA4 is a potent CAMKIIγ inhibitor.
TumCG↓, PA4 significantly impeded tumor growth in vivo in a xenograft T-cell lymphoma mouse model.
cMyc↓, PA4 reduced c-Myc levels and induced ROS in lymphoma cells
ROS↑,
UPR↑, Unfolded protein response (UPR) was elevated after PA4 treatment
ER Stress↑, UPR induces ER stress
PERK↑, PA4 treatment significantly increased protein kinase RNA-like ER kinase (PERK)
BioAv↑, Both BBM and PA4 were rapidly absorbed into the blood and detected 5 minutes after oral administration.
toxicity↓, mice received oral gavage with 50 mg/kg PA4 daily for 12 consecutive days (n = 6). After 12 days, there were no mortalities and no significant reductions in body weight (Figure 7D). Serum alanine aminotransferase and aspartate aminotransferase levels

3508-

Bor,

The Effect of Boron on the UPR in Prostate Cancer Cells is Biphasic

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

ER Stress↑, Treatment with 250 uM B induced endoplasmic reticulum (ER) stress in androgen dependent LNCaP and androgen independent DU-145 prostate cancer cell lines.
GRP78/BiP↑, this treatment induced BiP/GRP78, calreticulin and phosphorylation of eif2α the hallmarks of the unfolded protein response (UPR).
p‑eIF2α↑,
UPR↑,
eff↓, In contrast, concentrations of 1 uM B and 10 uM B rescued DU-145 cells respectively treated with 120 uM tunicamycin or 10 uM thapsigargin to induce ER stress.

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.

5862-

carbop,

Cisplatin,

Molecular Mechanisms of Resistance and Toxicity Associated with Platinating Agents

Review,

Var,

DNAdam↑, It is generally agreed that DNA is the preferential and cytotoxic target for cisplatin and other platinating agents. able to induce similar numbers of single-strand and double-strand breaks on DNA
ER Stress↑, shown to cause activation of apoptotic caspases through activation of the endoplasmic reticulum (ER) stress pathway (
UPR↑, When the ER experiences stress such as starvation or treatment with inhibitors of N-glycosylation (e.g. tunicamycin), it cannot fold or transport proteins correctly, and the UPR is activated.
ATF4↑, regulatory components of the ER stress pathway, including ATF4, ATF6, XBP1, and BiP (Grp78), are upregulated
ATF6↑,
XBP-1↑,
GRP78/BiP↑,
NP/CIPN↝, Carboplatin is notably less neurotoxic than cisplatin at conventional doses, with a similar sensory neuropathy occurring in approximately 6% of patients
toxicity↝, Carboplatin rarely results in nephrotoxicity and peripheral neuropathy, with its major toxicity being myelosuppression
eff↑, exposure to buthiomine sulfoximine (BSO), which significantly depleted cellular glutathione concentration, resulted in a significant enhancement in cisplatin cytotoxicity [151].
TrxR1⇅, Both cisplatin and transplatin show this inhibition of TxrR1 [161], as does oxaliplatin but not carboplatin [162]

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

2782-

CHr,

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Review,

Var,

Review,

Stroke,

Review,

Park,

*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

2790-

CHr,

Chrysin: Pharmacological and therapeutic properties

Review,

Var,

*hepatoP↑, graphical abstract
*neuroP↓,
*ROS↓,
*cardioP↑,
*Inflam↓,
eff↑, suppression of hTERT and cyclin D1 gene expression in T47D breast cancer cell lines is due to the combined effect of metformin and chrysin
hTERT/TERT↓,
cycD1/CCND1↓,
MMP9↓, nanoparticle-based chrysin in C57B16 mice bearing B16F10 melanoma tumors was markedly presented reductions in the levels of MMP-9, MMP-2, and TERT genes, whereas it enhanced TIMP-2 andTIMP-1 genes expression
MMP2↓,
TIMP1↑,
TIMP2↑,
BioAv↑, nano-encapsulation of chrysin and curcumin improved the delivery of these phytochemicals that significantly inhibited the growth of cancer cells, while it decreased the hTERT gene expression via increased solubility and bioavailability
HK2↓, chrysin treatment restrained tumor growth in HCC xenograft models and significantly reduced HK-2 expression in tumor tissue
ROS↑, showing a significant increase in intracellular reactive oxygen species (ROS), cytotoxicity, mitochondrial membrane potential (MMP) collapse, caspase-3 activation, ADP/ATP ratio, and ultimately apoptosis
MMP↓,
Casp3↑,
ADP:ATP↑,
Apoptosis↑,
ER Stress↑, Likewise, chrysin encouraged endoplasmic reticulum (ER) stress via stimulation of unfolded protein response (UPR
UPR↑,
GRP78/BiP↝, (eIF2Î±), PRKR-like ER kinase (PERK) and 78 kDa glucose-regulated protein (GRP78).
eff↑, silibinin and chrysin synergistically inhibited growth of T47D BCC and downregulated the hTERT and cyclin D1 level
Ca+2↑, Primarily, increased ROS and cytoplasmic Ca 2+ levels alongside induction of cell death and loss of MMP are involved in inhibition of ovarian cancer through chrysin.

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↑,

132-

CUR,

Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

in-vitro,

Pca,

PC3

TumCCA↑, inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.
ROS↑, correlating with the upregulation of reactive oxygen species
TumAuto↑,
UPR↑, The upregulation of eIF2α in curcumin-treated cells, suggests activation of the UPR-associated PERK pathway
ER Stress↑,
Casp3↑, Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase.
Casp9↑,
Casp12↑,
PARP↑,
other↝, Curcumin-treated PC3 cells expressed 146 upregulated and 184 downregulated proteins when compared with control PC3 cells (treated with DMSO).
GRP78/BiP↑, GRP78 and the PDI family were upregulated by 1.69 and ≥1.25-fold respectively
PDI↑,
eIF2α↑, other upregulated proteins related to ER stress figure eukaryotic translation initiation factor 2A (EIF2A), with a significant fold change of 1.25,
other↝, downregulated antioxidant markers such as peroxiredoxin 6 (PRDX6) and protein DJ-1 (PARK7) with significant fold changes of –1.39 and –1.51, respectively

5070-

dietSTF,

A review of fasting effects on the response of cancer to chemotherapy

Review,

Var,

chemoP↑, Studies suggest that fasting before or during chemotherapy may induce differential stress resistance, reducing the adverse effects of chemotherapy and enhancing the efficacy of drugs.
ChemoSen↑,
*DNArepair↑, (1) repairing DNA damage in normal tissues (but not tumor cells);
*Apoptosis↓, preventing apoptosis-mediated damage to normal cells;
*CD8+↑, depleting regulatory T cells and improving the stimulation of CD8 cells;
UPR↑, accumulating unfolded proteins and protecting cancer cells from immune surveillance
eff↝, discuss how ‘fasting-mimicking diet’ as a modified form of fasting enables patients to eat a low calorie, low protein, and low sugar diet while achieving similar metabolic outcomes of fasting.
TumAuto↑, upregulating autophagy flux as a protection against damage to organelles and some cancer cells;

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 (

3204-

EGCG,

The Role of ER Stress and the Unfolded Protein Response in Cancer

Review,

Var,

BID↓, EGCG, a green tea polyphenol, induces ER stress-mediated apoptosis in colorectal cancer cells, an effect associated with BiP upregulation
UPR↑, Natural compounds have also been identified as BiP modulators, including palmatine and epigallocatechin gallate (EGCG), which impair BiP function, leading to unfolded protein accumulation and UPR activation.
ER Stress↑,

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↑,

3207-

EGCG,

EGCG Enhances the Chemosensitivity of Colorectal Cancer to Irinotecan through GRP78-MediatedEndoplasmic Reticulum Stress

in-vitro,

CRC,

RKO

in-vitro,

CRC,

HCT116

GRP78/BiP↑, Findings showed that EGCG alone or in combination with irinotecan can significantly promote intracellular GRP78 protein expression, reduce mitochondrial membrane potential and intracellular ROS in RKO and HCT 116 cells
MMP↓,
ER Stress↑, activate ERS of colorectal cancer cells,
ROS↓, EGCG Alone and in Combination with Irinotecan Inhibit ROS Production in CRC
UPR↑, EGCG can promote the transformation of constitutive UPR of colorectal cancer cells into endoplasmic reticulum stress by increasing the accumulation of intracellular GRP78 and inhibiting its cell membrane translocation.

3208-

EGCG,

Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α

in-vitro,

Colon,

HT29

in-vitro,

Nor,

3T3

TumCD↓, EGCG treatment was toxic to the HT-29 cell line
ER Stress↑, EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and IRE1α
GRP78/BiP↑,
PERK↑,
eIF2α↑,
ATF4↑,
IRE1↑,
Apoptosis↑, Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity.
Casp3↑,
Casp7↑,
Wnt↓, (CRC) via suppression of the Wnt/β-catenin pathway
β-catenin/ZEB1↓,
*toxicity∅, This embryonic fibroblast cell line (3T3) has shown that the EGCG was not toxic to normal healthy cells, given the treatment at any concentration even at the highest concentration of EGCG (1000 μM).
UPR↑, ER stress is induced by EGCG and activates UPR proteins

5519-

EP,

Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions

Review,

Var,

MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

2860-

FIS,

Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways

in-vitro,

PC,

PANC1

in-vitro,

PC,

Bxpc-3

in-vitro,

Nor,

hTERT-HPNE

in-vivo,

NA,

mice

AMPK↑, We found that the AMPK/mTOR signaling pathway was enhanced after fisetin treatment
mTOR↑,
UPR↑, RNA-seq analysis revealed that the unfolded protein response pathway, which is activated by ER stress, was enriched
ER Stress↑, Fisetin induced ER stress in pancreatic cancer cells
selectivity↑, results showed that fisetin was less cytotoxic to normal cells compared with pancreatic cancer cells
TumCP↓, fisetin inhibited the proliferation of PANC-1 cells
PERK↑, expression of PERK, ATF4, and ATF6 were also upregulated by fisetin
ATF4↑,
ATF6↑,

2517-

H2,

Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response

in-vitro,

Var,

A549

in-vitro,

NA,

HCT116

in-vitro,

NA,

HeLa

in-vitro,

NA,

HepG2

in-vitro,

NA,

HT1080

in-vitro,

NA,

PC3

in-vitro,

NA,

SH-SY5Y

TumCP↓, the proliferation of four cell lines (A549, HeLa, HT1080, and PC3 cells) was increased 1.16–1.27-fold by 5% hydrogen gas, and 1.30–1.41-fold by 10% hydrogen
other↝, responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders.
eff↝, Effects of Hydrogen on Cell Proliferation Are Independent of Concentrations of Cellular Reactive Oxygen Species (ROS)
mt-UPR↑, hydrogen induces mtUPR as evidenced by upregulation of mtUPR-related molecules (ATF5, p-eIf2α, and HSP60) in the responders

4633-

HT,

Unlocking the effective alliance of β-lapachone and hydroxytyrosol against triple-negative breast cancer cells

in-vitro,

BC,

AntiCan↑, Hydroxytyrosol (HT) is a phenolic compound derived from olive trees with important anticancer properties that include the inhibition of cancer stem cells (CSCs)
CSCs↓,
antiOx↑, and metastatic features in TNBC, as well as relevant antioxidant activities by mechanisms such as the induction of NQO1.
NQO1↑,
TumCCA↑, HT exhibits anti-proliferative, pro-apoptotic, and cell cycle arrest effects in several TNBC cells, including docetaxel-resistant TNBC cells.
ER Stress↑, combination's anticancer activity is linked to a strong induction of endoplasmic reticulum stress and apoptosis through the unfolded protein response.
Apoptosis↑,
UPR↑, combination of β-LP and HT dramatically impacts protein folding, activating the unfolded protein response (UPR) and programmed cell death through apoptosis in response to ER stress.

601-

HT,

Dihydroxyphenylethanol induces apoptosis by activating serine/threonine protein phosphatase PP2A and promotes the endoplasmic reticulum stress response in human colon carcinoma cells

in-vivo,

NA,

HT-29

TumCG↓,
Apoptosis↑,
ER Stress↑,
UPR↑,
CHOP↑,
JNK↑,
TNF-α↓,
PPP2R1A↑, DPE specifically activates PP2A

4292-

LT,

Luteolin for neurodegenerative diseases: a review

Review,

AD,

Review,

Park,

Review,

MS,

Review,

Stroke,

*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

2903-

LT,

Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma

in-vitro,

GBM,

U251

in-vitro,

GBM,

U87MG

in-vivo,

NA,

mouse

ER Stress↑, Luteolin induced a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells by increasing intracellular reactive oxygen species (ROS) levels.
ROS↑,
PERK↑, Luteolin induced expression of ER stress-associated proteins, including phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12.
eIF2α↑,
ATF4↑,
CHOP↑,
Casp12↑,
eff↓, Inhibition of ROS production by anti-oxidant N-acetylcysteine could reverse luteolin-induced ER stress and mitochondrial pathways activation as well as apoptosis.
UPR↑, Researches indicate that abnormalities in ER function can cause ER stress, resulting in unfolded protein response (UPR),
MMP↓, integrity of mitochondrial membranes potential decreased in U87MG cells after treatment of 40 uM luteolin
Cyt‑c↑, release of cytochrome C to cytoplasm was elevated in U251MG cells
Bcl-2↓, significantly decreased the expression of anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax in U251MG and U87MG glioblastoms cells.
BAX↑,
TumCG↓, Luteolin inhibited tumor growth in a xenograft mouse model
Weight∅, luteolin did not affect body weight, alanine aminotransferase (ALT) or aspartate transaminase (AST)
ALAT∅,
AST∅,

3457-

MF,

Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis

Review,

Var,

Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

3458-

MF,

Magnetic Control of Protein Expression via Magneto-mechanical Actuation of ND-PEGylated Iron Oxide Nanocubes for Cell Therapy

in-vitro,

GBM,

65 mT and 50 Hz for 30 min

ER Stress↑, Western blot studies indicated actuated, intracellular cubic ND-PEG-SPIONs can cause mild ER stress at short periods (up to 3 h) of postmagnetic field treatment thus leading to the unfolded protein response
UPR↑,
Ca+2↑, Studies have shown that applying low-frequency magnetic fields (50 Hz) to young rats leads to stimulation of Ca2+ channel transport and therefore increases intracellular Ca2+ levels.
TRAIL↓, n the present study, we observed a similar effect where MMA caused ER stress, which resulted in a decrease in TRAIL secretion in tC17.2 stem cells
GRP78/BiP↑, A slight expression increase was also noted for the other chaperone, GRP78, for all treatment conditions.

4643-

OLE,

HT,

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

Review,

Var,

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

1664-

PBG,

Anticancer Activity of Propolis and Its Compounds

Review,

Var,

Apoptosis↑,
TumCMig↓,
TumCCA↑,
TumCP↓,
angioG↓,
P21↑, upregulating p21 and p27 expression
p27↑,
CDK1↓, thanol-extracted Cameroonian propolis increased the amount of DU145 and PC3 cells in G0/G1 phase, down-regulated cell cycle proteins (CDK1, pCDK1, and their related cyclins A and B)
p‑CDK1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
P70S6K↓, Caffeic acid phenylethyl ester has been shown to inhibit the S6 beta-1 ribosomal protein kinase (p70S6K),
CLDN2↓, inhibition of NF-κB may be involved in the decrease of claudin-2 mRNA level
HK2↓, Chinese poplar propolis has been shown to significantly reduce the level of glycolysis at the stage of action of hexokinase 2 (HK2), phosphofructokinase (PFK), muscle isozyme pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
PFK↓,
PKM2↓,
LDHA↓,
TLR4↓, hinese propolis, as well as CAPE, inhibits breast cancer cell proliferation in the inflammatory microenvironment by inhibiting the Toll-like receptor 4 (TLR4) signal pathway
H3↓, Brazilian red propolis bioactive isoflavonoid, down-regulates the alpha-tubulin, tubulin in microtubules, and histone H3 genes
α-tubulin↓,
ROS↑, CAPE also affects the apoptotic intrinsic pathway by increasing ROS production
Akt↓, CAPE induces apoptosis by decreasing the levels of proteins related to carcinogenesis, including Akt, GSK3b, FOXO1, FOXO3a, NF-kB, Skp2 and cyclin D1
GSK‐3β↓,
FOXO3↓,
NF-kB↓,
cycD1/CCND1↓,
MMP↓, It was found that chrysin caused a loss of mitochondria membrane potential (MMP) while increasing the production of reactive oxygen species (ROS), cytoplasmic Ca2+ levels, and lipid peroxidation
ROS↑,
i-Ca+2↑,
lipid-P↑,
ER Stress↑, Chrysin also induced endoplasmic reticulum (ER) stress by activating unfolded protein response proteins (UPR) such as PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78)
UPR↑,
PERK↑,
eIF2α↑,
GRP78/BiP↑,
BAX↑, CAPE activated Bax protein
PUMA↑, CAPE also significantly increased PUMA expression
ROS↑, Northeast China causes cell apoptosis in human gastric cancer cells with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential.
MMP↓,
Cyt‑c↑, release of cytochrome C from mitochondria to the cytoplasm is observed, as well as the activation of cleaved caspases (8, 9, and 3) and PARP
cl‑Casp8↑,
cl‑Casp8↑,
cl‑Casp3↑,
cl‑PARP↑,
eff↑, administration of Iranian propolis extract in combination with 5-fluorouracil (5-FU) significantly reduced the number of azaxymethane-induced aberrant crypt foci compared to 5-FU or propolis alone.
eff↑, Propolis may also have a positive effect on the efficacy of photodynamic therapy (PDT). enhances the intracellular accumulation of protoporphyrin IX (PpIX) in human epidermoid carcinoma cells
RadioS↑, breast cancer patients undergoing radiotherapy and supplemented with propolis had a statistically significant longer median disease-free survival time than the control group
ChemoSen↑, confirmed that propolis mouthwash is effective and safe in the treatment of chemo- or radiotherapy-induced oral mucositis in cancer patients.
eff↑, Quercetin, ferulic acid, and CAPE may also influence the MDR of cancer cells by inhibiting P-gp expression

4951-

PEITC,

ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

in-vitro,

Ovarian,

PA1

5 μM

in-vitro,

Ovarian,

SKOV3

ROS↑, PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH) depletion in SKOV-3.
TumCP↓,
GSH↓, One of the generating ROS mechanisms by PEITC is a depletion of GSH
selectivity↑, However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells
UPR↑, PEITC Induces Unfolded Protein Response, Attenuated by NAC, in Ovarian Cancer Cells
CHOP↑, The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and endoplasmic reticulum resident chaperone BiP/GRP78 were parallely up-regulated
ER Stress↑,
GRP78/BiP↑,
PERK↑, with activation of two major sensors of the UPR [PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3) in response to ROS accumulation induced by PEITC (5 μM)
ATF6↑,
eff↓, ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78)
TumCG↓, PEITC Inhibits Growth of Ovarian Cancer Cells without Inhibiting the Growth of Normal PBMC Cells
Apoptosis↑, PEITC Induces Apoptotic Cell Death in Ovarian Cancer Cell Lines
toxicity↓, IC50 value of PEITC for endothelial cells was more than 100 μM, suggesting cancer cell-specific cell death by PEITC (28). PEITC is a well-known ROS inducer in cancer cells without any potential adverse effect on normal cells (

1943-

PL,

Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells

in-vitro,

GBM,

0-10 μM

in-vivo,

NA,

mice

selectivity↑, Piperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells.
ROS↑,
selectivity↑, piperlongumine treatment in HGG cells, but not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4), an ROS-reducing enzyme that is overexpressed in HGGs
Prx4↓, Piperlongumine Inactivates PRDX4 in HGG Cells
*Prx4∅,
ER Stress↑, Moreover, piperlongumine exacerbated intracellular ER stress
CHOP↑, We found that piperlongumine treatment rapidly and substantially increased CHOP protein levels in all 4 HGG sphere cultures
UPR↑, As with CHOP, other UPR protein levels were also increased upon piperlongumine treatment

3065-

RES,

Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

in-vitro,

lymphoma,

0-200uM

UPR↑, treatment with RES lead to the activation of all 3 branches of the UPR
IRE1↑, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing
p‑eIF2α↑,
PERK↑,
ATF6↑,
GRP78/BiP↑, increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines.
GRP94↑,
CHOP↑,
GADD34↑, RES induces a pathway initiated by phosphorylation of eIF2α and followed by the upregulation of GADD34 and ATF4.
ATF4↑,
XBP-1↑, RES increased XBP-1 expression both in Raji and in Daudi cells
Ca+2↑, RES was found to significantly increase cytosolic Ca2+
ER Stress↑, RES was able to induce ER stress and activated all 3 branches of the UPR.

3066-

RES,

Resveratrol triggers ER stress-mediated apoptosis by disrupting N-linked glycosylation of proteins in ovarian cancer cells

GSK‐3β↑, resveratrol suppressed the hexosamine biosynthetic pathway and interrupted protein glycosylation through GSK3β activation
Akt↓, Akt attenuation in response to resveratrol.
CHOP↑, Resveratrol-mediated disruption of protein glycosylation induced cellular apoptosis as indicated by the up-regulation of GADD153, followed by the activation of ER-stress sensors (PERK and ATF6α).
ER Stress↑,
PERK↑,
ATF6↑,
UPR↑, Disruption of protein glycosylation causes the accumulation of aberrant of proteins in the endoplasmic reticulum (ER) which in turn activates unfolded protein responses (UPR) in the ER, leading to severe stressful conditions
GlucoseCon↓, Previous studies have shown that resveratrol (RSV) impairs glucose consumption via Akt/GLUT1 axis in cancer [

3002-

RosA,

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

Review,

Var,

TumCG↓, SW480 colon cancer cells and found RE to significantly decrease cell growth at a concentration of 31.25 µg/mL (48 h),
TumCP↓, Cell proliferation was dramatically decreased and cell cycle arrest was induced in HT-29 and SW480 c
TumCCA↑,
ChemoSen↑, RE enhanced the inhibitory effects of the chemotherapeutic drug 5-fluorouracil (5-FU) on proliferation and sensitized 5-FU resistant cells
NRF2↑, HCT116 ↑ Nrf2, ↑ PERK, ↑ sestrin-2, ↑ HO-1, ↑ cleaved-casp 3
PERK↑,
SESN2↑,
HO-1↑,
cl‑Casp3↑,
ROS↑, HT-29 ↑ ROS accumulation, ↑ UPR, ↑ ER-stress
UPR↑,
ER Stress↑,
CHOP↑, HT-29: ↑ ROS levels, ↑ HO-1 and CHOP
HER2/EBBR2↓, SK-BR-3: ↑ FOS levels, ↑ PARP cleavage, ↓ HER2, ↓ ERBB2, ↓ ERα receptor.
ER-α36↓,
PSA↓, LNCaP : ↑ CHOP, ↓ PSA production, ↑ Bax, ↑ cleaved-casp 3, ↓ androgen receptor expression
BAX↑,
AR↓,
P-gp↓, A2780: ↓ P-glyco protein, ↑ cytochrome c gene, ↑ hsp70 gene
Cyt‑c↑,
HSP70/HSPA5↑,
eff↑, This study noted that the rosemary essential oil was more potent than its individual components (α-pinene, β-pinene, 1,8-cineole) when tested alone at the same concentrations.
p‑Akt↓, A549: ↓ p-Akt, ↓ p-mTOR, ↓ p-P70S6K, ↑ PARP cleavage
p‑mTOR↓,
p‑P70S6K↓,
cl‑PARP↑,
eff↑, RE containing 10 µM equivalent of CA, or 10 µM CA alone (96 h) potentiated the ability of vitamin D derivatives to inhibit cell viability and proliferation, induce apoptosis and cell cycle arrest and increase differentiation of WEHI-3BD murine leukem

4996-

Sal,

The Molecular Basis for Inhibition of Stemlike Cancer Cells by Salinomycin

CSCs↓, The natural product salinomycin, a K+ -selective ionophore, was recently found to exert selectivity against such cancer stem cells.
selectivity↑,
Wnt↓, This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear.
ERStress↑, accumulation in the endoplasmic reticulum (ER).
Ca+2↓, This localization is connected to induction of Ca2+ release from the ER into the cytosol.
UPR↑, Depletion of Ca 2+ from the ER induces the unfolded protein response a
CHOP↑, salinomycin-induced ER Ca2+ depletion up-regulates C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin.
β-catenin/ZEB1↓,
CD44↓, alinomycin efficiently and selectively reduced the proportion of breast cancer CD44 + /CD24− cells, a phenotype associated with enhanced tumorigenic capacity.
CD24↓,
PKCδ↑, Salinomycin Induces ER Ca2+ Release, ER Stress, and PKC Activation

4908-

Sal,

Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling

in-vitro,

Pca,

PC3

0, 2, 5, 10, 20 and 50 µM

in-vitro,

Pca,

DU145

tumCV↓, salinomycin inhibited the viability and induced the apoptosis of PC-3 and DU145 cells in a dose-dependent manner
ROS↑, salinomycin increased the production of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and the lipid peroxidation.
lipid-P↑,
UPR↑, salinomycin induced the activation of unfolded protein response and endoplasmic reticulum stress in DU145 and PC-3 cells
ER Stress↑,
NRF2↓, salinomycin significantly downregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone dehydrogenase 1
NADPH↓,
HO-1↓,
SOD↓, and decreased the activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in PC-3 and DU145 cells.
Catalase↓,
GPx↓,
eff↓, Nrf2 activator, tert-butylhydroquinone, significantly reversed the therapeutic effects of salinomycin by stimulating the Nrf2 pathway and increasing the activity of antioxidant enzymes.
TumCP↓, proliferation of PC-3 and DU145 cells was significantly decreased following treatment with salinomycin (2-50 µM

5125-

Sal,

Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma

in-vitro,

GBM,

ER Stress↑, SLM induces a potent endoplasmic reticulum (ER) stress followed by the trigger of the unfolded protein response (UPR) and an aberrant autophagic flux that culminated in necrosis due to mitochondria and lysosomal alterations.
UPR↑,
autoF↓, SLM treatment does not trigger apoptosis and blocks the autophagy flux in glioma cell line
lysosome↝,
ROS↑, aberrant autophagic flux was orchestrated by the production of Reactive Oxygen Species (ROS)
lipid-P↑, our data suggest that in our system the oxidative stress blocks the autophagic flux through lipid oxidation.
CSCs↓, SLM induces a potent antitumor effect in brain tumor stem cells (BTSCs) and established adult and pediatric glioma cell lines in vitro
necrosis↑, SLM induces necrosis cell death
ATP↓, with increasing doses of SLM displayed a decrease in intracellular ATP levels
MMP↓, SLM treated cells displayed significantly lower ΔΨm than untreated cells
MOMP↑, SLM induces mitochondrial MOMP.
DNAdam↑, We observed double strand breaks in SLM-treated cells (Figure 4C) and it is possible that this DNA damage is induced as a consequence of AIF internalization.
AIF↑,
lysoMP↑, hypothesis that SLM treatment triggers an autophagic process that cannot proceed adequately because of LMP resulting from oxidative stress.
MitoP↑, In addition, impairment of mitochondrial activity would trigger mitophagy, with engulfment of the organelle and initiation of autophagy.
Ca+2↑, The elevated levels of calcium and ROS inside mitochondria results in MOMP

3180-

SFN,

Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts

Review,

Var,

*cardioP↑, broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis,
*ER Stress↓, through the amelioration of ER stress in both in vivo and in vitro studies.
GRP78/BiP↑, Sulforaphane significantly increased the level of Bip/GRP78, and XBP-1 protein expression and enhanced the rate of HepG2 cells apoptosis.
XBP-1↑,
Apoptosis↑,
*NRF2↑, Mitigates oxidative stress and ER stress in vascular cells, contributing to cardioprotection
UPR↑, SFN can drive the UPR into an overactivated state(ai)

1002-

SSE,

Osi,

Adag,

Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference

in-vitro,

Lung,

H1975

7uM@72hr

in-vitro,

Lung,

H385

6uM@72hr

Apoptosis↑,
Ferroptosis↑,
DNMT1↓,
TET1↑,
TumCCA↑, G2/M arrest
cl‑PARP↑,
cl‑Casp3↑, H1975 cells only
Cyt‑c↑,
BIM↑,
NOXA↑,
Apoptosis↑,
ROS↑, Selenite is associated with oxidative stress
ER Stress↑, H1975 cells only
UPR↑, H1975 cells only

3957-

Taur,

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

*UPR↑, together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality.
*Inflam↓, modulating inflammation [133,134], and acting as an antioxidant in scavenging free radicals [135,136] and in reducing apoptosis
*antiOx↑,
*ROS↓,
*Apoptosis↓,
*Ca+2↓, Taurine exerts its neuroprotective effect through maintenance of the structural integrity of the membrane that leads to decreases in the intracellular Ca2+ levels
*neuroP↑, As a neuroprotective molecule, its alleviation of protein aggregation leads to improvement in neuronal function, thereby averting the neuronal damage that reduces brain functioning in different NDs

Showing Research Papers: 1 to 48 of 48

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 48

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 260

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 2, GPx1↑, 1, GPx4↑, 1, GSH↑, 1, HO-1↑, 1, MDA↓, 1, MPO↓, 1, NRF2↑, 4, Prx4∅, 1, ROS↓, 6, ROS↑, 1, SOD↑, 2, SOD1↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis ⓘ

CREB↑, 1, glucose↓, 1, LDL↓, 1, lipidLev↓, 1, PPARγ↑, 1, SIRT1↑, 1,

Cell Death ⓘ

Akt↓, 1, Apoptosis↓, 2, BAX↓, 1, Bax:Bcl2↓, 1, Casp3↓, 1, Casp9↑, 1, Cyt‑c↓, 1, iNOS↓, 1, JNK↑, 1,

Protein Folding & ER Stress ⓘ

CHOP↑, 1, cl‑eIF2α↑, 1, ER Stress↓, 1, GRP78/BiP↓, 1, GRP78/BiP↑, 2, p‑PERK↑, 1, UPR↓, 1, UPR↑, 3,

DNA Damage & Repair ⓘ

DNArepair↑, 1,

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1, PI3K↓, 1,

Migration ⓘ

Ca+2?, 1, Ca+2↓, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1β↓, 1, IL2↓, 1, IL33↓, 1, IL6↓, 1, IL8↓, 1, Inflam↓, 6, NF-kB↓, 3, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1, tau↓, 1, TrkB↑, 1,

Protein Aggregation ⓘ

Aβ↓, 1, BACE↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↝, 1, eff↑, 1,

Clinical Biomarkers ⓘ

AST↓, 1, BloodF↑, 1, IL6↓, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, cachexia↑, 1, cardioP↑, 4, chemoP↑, 1, cognitive↑, 2, hepatoP↑, 2, memory↑, 2, neuroP↓, 1, neuroP↑, 4, RenoP↑, 1, toxicity?, 1, toxicity↓, 1, toxicity↝, 1, toxicity∅, 1,

Infection & Microbiome ⓘ

AntiViral↑, 1, CD8+↑, 1,
Total Targets: 81

Scientific Paper Hit Count for: UPR, Unfolded Protein Response

5 EGCG (Epigallocatechin Gallate)
4 Silver-NanoParticles
4 Chrysin
3 HydroxyTyrosol
3 salinomycin
2 Luteolin
2 Magnetic Fields
2 Resveratrol
1 Vitamin C (Ascorbic Acid)
1 Allicin (mainly Garlic)
1 Alpha-Lipoic-Acid
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Baicalein
1 Berbamine
1 Boron
1 Bortezomib
1 carboplatin
1 Cisplatin
1 Cannabidiol
1 Curcumin
1 diet Short Term Fasting
1 Electrical Pulses
1 Fisetin
1 Hydrogen Gas
1 Oleuropein
1 Propolis -bee glue
1 Phenethyl isothiocyanate
1 Piperlongumine
1 Rosmarinic acid
1 Sulforaphane (mainly Broccoli)
1 Selenite (Sodium)
1 Osimertinib
1 Adagrasib
1 Taurine

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

UPR Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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