JNK Cancer Research Results

JNK, c-Jun N-terminal kinase (JNK): Click to Expand ⟱

Source:

Type:

JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. Janus signaling promotes cancer cell survival.
JNK, or c-Jun N-terminal kinase, is a member of the mitogen-activated protein kinase (MAPK) family. It plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). JNK is activated in response to various stress signals, such as UV radiation, oxidative stress, and inflammatory cytokines.
JNK activation can promote apoptosis in cancer cells, acting as a tumor suppressor. However, in other contexts, it can promote cell survival and proliferation, contributing to tumor progression.

JNK is often unregulated in cancers, leading to increased cancer cell proliferation, survival, and resistance to apoptosis. This activation is typically associated with poor prognosis and aggressive tumor behavior.

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

4557-

AgNPs,

The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells

in-vitro,

NA,

NIH-3T3

in-vitro,

CRC,

HCT116

Cyt‑c↑, Treatment with nanosilver induced the release of cytochrome c into the cytosol and translocation of Bax to mitochondria, indicating that nanosilver-mediated apoptosis is mitochondria-dependent.
ROS↑, Nanosilver-induced apoptosis was associated with the generation of reactive oxygen species (ROS) and JNK activation, and inhibition of either ROS or JNK attenuated nanosilver-induced apoptosis.
JNK↑,

324-

AgNPs,

CPT,

Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells

in-vitro,

Cerv,

HeLa

ROS↑,
Casp3↑,
Casp9↑,
Casp6↑,
GSH↓,
SOD↓,
GPx↓,
MMP↓, loss of
P53↑,
P21↑,
Cyt‑c↑,
BID↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
Akt↓,
Raf↓,
ERK↓,
MAP2K1/MEK1↓,
JNK↑,
p38↑,

369-

AgNPs,

Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

in-vitro,

Liver,

ROS↑,
GSH↓,
DNAdam↑,
lipid-P↝, damage
Apoptosis↑,
BAX↑,
Bcl-2↓,
MMP↓, disruption
Casp9↑,
Casp3↑,
JNK↑,

363-

AgNPs,

Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

ROS↑,
lipid-P↑, lipid membrane peroxidation
Apoptosis↑,
BAX↑,
Bcl-2↓,
MMP↓, disruption
Cyt‑c↑, release from mitochondria
Casp3↑,
Casp9↑,
JNK↑,

2655-

AL,

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

Review,

GC,

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

2666-

AL,

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

Review,

Var,

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

248-

AL,

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

in-vitro,

GBM,

U87MG

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

3442-

ALA,

α‑lipoic acid modulates prostate cancer cell growth and bone cell differentiation

in-vitro,

Pca,

22Rv1

in-vitro,

Pca,

C4-2B

in-vitro,

Nor,

3T3

tumCV↓, Notably, α‑LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose‑dependent manner.
TumCMig↓,
TumCI↓,
ROS↑, α‑LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF‑1α expression, which started the downstream molecular cascade and activated JNK/caspase‑3 signaling pathway
Hif1a↑, The expression of HIF-1α significantly increased following α-LA treatment and was comparable with the changes in ROS.
JNK↑,
Casp↑,
TumCCA↑, arrest of the cell cycle in the S‑phase, which has led to apoptosis of PCa cells
Apoptosis↑,
selectivity↑, Also, the treatment of α‑LA improved bone health by reducing PCa‑mediated bone cell modulation.

277-

ALA,

α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation

in-vitro,

Pca,

22Rv1

 500 μM

in-vitro,

Pca,

C4-2B

ROS↑, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway.
Hif1a↑, HIF-1α, is a key regulator in response to cellular stressors, and excessive ROS levels can influence its expression. (HIF-1α) is essential for the physiological response to hypoxia(resulting from elevated intracellular ROS levels)
JNK↑,
Casp3↑,
P21↑,
BAX↑,
Bcl-xL↓,
cFos↓,

259-

ALA,

Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells

in-vitro,

Liver,

HepG2

500 µM for 24, 48 and 72 h

in-vitro,

Liver,

FaO

Cyc↓, cyclin A
P21↑,
ROS↑, α-LA treatment at a concentration that induces apoptosis (500 µM) caused increased ROS generation in FaO cells, as early as 1 h after treatment with a further increase at 3 and 6 h.
p‑P53↑,
BAX↑, 500 µM α-LA produced an increase in Bax levels as early as 24 h
Cyt‑c↑, release from mitochondria
Casp↑, Treatment of HepG2 cells with 500 µM α-LA caused a time-dependent activation of caspase-3, as indicated by a progressive decrease of levels of pro-caspase-3
survivin↓,
JNK↑,
Akt↓,

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↑,

584-

Api,

Cisplatin,

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms

in-vivo,

Var,

Eighty Swiss albino male mice

Beclin-1↑, 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities
Casp3↑,
Casp9↑,
JNK↑,
Mcl-1↓, significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity
Ki-67↓, alleviated the histopathological changes with significant decrease of Ki-67 proliferation index

270-

Api,

Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo via inactivation of Akt and activation of JNK

in-vivo,

AML,

U937

 20-40 uM (12/24h)

Akt↓, nactivation of Akt and activation of JNK
JNK↑,
Mcl-1↓,
cl‑Bcl-2↓, cleavage
Casp3↑,
Casp7↑,
Casp9↑,
cl‑PARP↑, cleaved
mTOR↓,
GSK‐3β↓,

3383-

ART/DHA,

Dihydroartemisinin: A Potential Natural Anticancer Drug

Review,

Var,

TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

3166-

Ash,

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives

Review,

Var,

*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

2606-

Ba,

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

Review,

HCC,

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

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

1390-

BBR,

Rad,

Berberine Inhibited Radioresistant Effects and Enhanced Anti-Tumor Effects in the Irradiated-Human Prostate Cancer Cells

in-vitro,

Pca,

PC3

RadioS↑, cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone
Apoptosis↑,
ROS↑, ROS generation was elevated by berberine with or without irradiation.
eff↑, antioxidant NAC inhibited berberine and radiation-induced cell death.
BAX↑,
Casp3↑,
P53↑,
p38↑,
JNK↑,
Bcl-2↓,
ERK↓,
HO-1↓,

1386-

BBR,

Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

tumCV↓,
ROS↑,
JNK↑,
MMP↓,
Bcl-2↓,
BAX↑,
Cyt‑c↑, increased the release of cytochrome c
AIF↝,

1378-

BBR,

Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway

in-vitro,

Lung,

Apoptosis↑,
Casp3↑,
Cyt‑c↑, cytochrome c release
MMP↓,
p‑JNK↑,
eff↓, N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to both suppress apoptosis signal-regulating kinase 1 (ASK1) and JNK activation and disrupt apoptotic induction.

1379-

BBR,

Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells

in-vitro,

lymphoma,

TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

2743-

BetA,

Betulinic acid and the pharmacological effects of tumor suppression

Review,

Var,

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

2775-

Bos,

The journey of boswellic acids from synthesis to pharmacological activities

Review,

Var,

Review,

AD,

Review,

PSA,

ROS↑, modulation of reactive oxygen species (ROS) formation and the resulting endoplasmic reticulum stress is central to BA’s molecular and cellular anticancer activities
ER Stress↑,
TumCG↓, Cell cycle arrest, growth inhibition, apoptosis induction, and control of inflammation are all the effects of BA’s altered gene expression
Apoptosis↑,
Inflam↓,
ChemoSen↑, BA has additional synergistic effects, increasing both the sensitivity and cytotoxicity of doxorubicin and cisplatin
Casp↑, BA decreases viability and induces apoptosis by activat- ing the caspase-dependent pathway in human pancreatic cancer (PC) cell lines
ERK↓, BA might inhibit the activation of Ak strain transforming (Akt) and extracellular signal–regulated kinase (ERK)1/2,
cl‑PARP↑, initiation of cleavage of PARP were prompted by the treatment with AKBA
AR↓, AKBA affects the androgen receptor by reducing its expression,
cycD1/CCND1↓, decrease in cyclin D1, which inhibits cellular proliferation
VEGFR2↓, In prostate cancer, the downregulation of vascular endothelial growth factor receptor 2–mediated angiogenesis caused by BA
CXCR4↓, Figure 6
radioP↑,
NF-kB↓,
VEGF↓,
P21↑,
Wnt↓,
β-catenin/ZEB1↓,
Cyt‑c↑,
MMP2↓,
MMP1↓,
MMP9↓,
PI3K↓,
MAPK↓,
JNK↑,
*5LO↓, Table 1 (non cancer)
*NRF2↑,
*HO-1↑,
*MDA↓,
*SOD↑,
*hepatoP↑, Preclinical studies demonstrated hepatoprotective impact for BA against different models of hepatotoxicity via tackling oxidative stress, and inflammatory and apoptotic indices
*ALAT↓,
*AST↓,
*LDH↑,
*CRP↓,
*COX2↓,
*GSH↑,
*ROS↓,
*Imm↑, oral administration of biopolymeric fraction (BOS 200) from B. serrata in mice led to immunostimulatory effects
*Dose↝, BA at low concentration tend to stimulate an immune response, as those utilized in the study of Beghelli et al. (2017) however, utilizing higher concentration suppressed the immune response
*eff↑, Useful actions on skin and psoriasis
*neuroP↑, AKBA has substantially diminished the levels of inflammatory markers such as 5-LOX, TNF-, IL-6, and meliorated cognition in lipopolysaccharide-induced neuroinflammation rodent models
*cognitive↑,
*IL6↓,
*TNF-α↓,

5693-

BRU,

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

in-vivo,

HCC,

mouse Hepa-1c1c7 hepatoma cells

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

5697-

BRU,

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

in-vitro,

HNSCC,

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

5836-

CAP,

In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway

vitro+vivo,

PC,

AsPC-1

pancreatic tumor xenografts in athymic nude mice

in-vitro,

PC,

Bxpc-3

tumCV↓, Treatment of AsPC-1 and BxPC-3 cells with capsaicin resulted in a dose-dependent inhibition of cell-viability and induction of apoptosis
Apoptosis↑,
ROS↑, which was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential.
MMP↓,
eff↓, These effects were significantly blocked when the cells were pretreated with a general antioxidant N-acetyl cysteine (NAC).
BAX↑, Exposure of AsPC-1 and BxPC-3 cells to capsaicin was also associated with increased expression of Bax, down-regulation of bcl-2, survivin and significant release of cytochrome c and AIF in the cytosol.
Bcl-2↓,
survivin↓,
Cyt‑c↑,
AIF↑,
selectivity↑, above-mentioned effects were not observed in the normal acinar cells in response to capsaicin-treatment.
JNK↑, Capsaicin-treatment resulted in the activation of JNK and JNK inhibitor SP600125 afforded protection against capsaicin-induced apoptosis.
TumCG↓, Furthermore, capsaicin when given orally markedly suppressed the growth of AsPC-1 pancreatic tumor xenografts in athymic nude mice, without side effects.

5833-

CAP,

Capsaicin: From Plants to a Cancer-Suppressing Agent

Review,

Var,

chemoPv↑, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer.
TumCCA↑, The proposed anticancer mechanisms of capsaicin include an increase of cell-cycle arrest and apoptosis
Apoptosis↑,
ROS↑, Colo 205 150 Induced cell death, increased ROS and pro-apoptotic proteins
MMP↓, Human bladder cancer T24 100 Induced ROS production and mitochondrial membrane depolarization
Ca+2↑, capsaicin induces apoptosis in cancer cells is not completely elucidated but involves intracellular calcium increase, ROS, disruption of mitochondrial membrane transition potential, and activation of transcription factors such as NFκB and STATS (
JNK↑, studies performed in pancreatic cells showed that capsaicin apoptosis inducing effects were associated with ROS generation, JNK activation, mitochondrial depolarization, release of cytochrome c in the cytosol and activation of caspase-3 cascade
Casp3↑,
NADH↓, Capsaicin can also inhibit the plasma membrane NADH oxidase by functioning as a coenzyme Q antagonist.
CDK2↓, Capsaicin inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with the inhibition of CDK2, CDK4 and CDK6.
CDK4↓,
CDK6↓,
P53↑, capsaicin induces apoptosis in AGS cells through upregulation of p53 and that the apoptotic activity of capsaicin is p53-dependent.

2652-

CAP,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, capsaicin has been reported as both a chemopreventive and as an anticancer agent
AntiCan↑,
ROS↑, Capsaicin has been reported to induce ROS-dependent cell death in various cancers, including colorectal [63], prostate [64,65], bladder [66,67,68], and pancreatic [69,70] cancers.
TumCG↓, reported to inhibit tumor growth in vivo in mouse xenograft models of prostate [64] and bladder [66] cancers.
ROS↑, Mechanistically, capsaicin-mediated ROS accumulation
MMP↑, leads to mitochondrial membrane depolarization [63,64,66],
Apoptosis↑, which further triggers mitochondria-dependent apoptosis
TumCCA↑, as well as G0/G1 cell cycle arrest
JNK↑, in bladder cancer cells, capsaicin induces JNK activation in an ROS-dependent manner
SOD↓, (1) inhibition of the activity of antioxidant enzymes SOD, catalase (CAT), and glutathione peroxidase [70];
Catalase↓,
GPx↓,
other↓, (2) inhibition of the activity of mitochondrial complex-I and complex-III in the electron transport chain [70];
SIRT1↓, (3) downregulation of the expression of sirtuin-1, a NAD-dependent deacetylase that regulates the expression of various antioxidant enzymes [69];
NADPH↑, (4) upregulation of the expression of NADPH oxidase 4, which generates superoxide [69];
FOXO3↑, (5) increased expression of FOXO3a, which is a transcription factor that regulates the oxidative stress response [68].

2012-

CAP,

Capsaicin induces cytotoxicity in human osteosarcoma MG63 cells through TRPV1-dependent and -independent pathways

NA,

OS,

MG63

0-40 μM

20 μM

AntiTum↑, capsaicin induces apoptosis in various tumor cells as a mechanism of its anti-tumor activity
Apoptosis↑, capsaicin-induced apoptosis and the activation of transient receptor potential receptor vanilloid 1 (TRPV1) in a dose- and time-dependent manner in human osteosarcoma MG63 cells in vitro
TRPV1↑, TRPV1 activation is required for the capsaicin-induced overproduction of ROS and decrease in SOD activity
ROS↑, overproduction of reactive oxygen species (ROS)
SOD↓, decrease in superoxide dismutase (SOD) activity
AMPK↑, capsaicin induced the activation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK), p53 and C-jun N-terminal kinase (JNK)
P53↑,
JNK↑,
Bcl-2↓, decrease in the level of B-cell lymphoma 2 (Bcl-2)
Cyt‑c↑, increase in the levels of Cytochrome C
cl‑Casp3↑, cleaved-caspase-3
cl‑PARP↑, cleaved polyadenosine diphosphate-ribose polymerase (PARP) in a time-dependent manner following capsaicin treatment in MG63 cells
Ca+2↑, Once the channel is activated, it can enable the rapid increase of intracellular calcium (Ca2+) levels and initiate cell death
MMP↓, several independent studies have demonstrated that capsaicin disrupted MMP (Δψm)

2019-

CAP,

Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer

Review,

Var,

chemoPv↑, Capsaicin has shown significant prospects as an effective chemopreventive agent
Ca+2↑, Capsaicin was shown to cause upstream activation of Ca2+
antiOx↑, Another plausible mechanism implicated in the chemopreventive action of capsaicin is its anti-oxidative effects.
*ROS↓, capsaicin inhibits ROS release and the subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxidized low-density lipoprotein in normal human HUVEC cells
*MMP∅,
*Cyt‑c∅,
*Casp3∅,
*eff↑, dietary curcumin and capsaicin concurrent administration in high-fat diet-fed rats were shown to mitigate the testicular and hepatic antioxidant status by increasing GSH levels, glutathione transferase activity, and Cu-ZnSOD expression
*Inflam↓, Anti-inflammation is another mechanism implicated in the chemopreventive action of capsaicin.
*NF-kB↓, inhibition of NF-kB by capsaicin
*COX2↓, compound elicits COX-2 enzyme activity inhibition and downregulation of iNOS
iNOS↓,
TRPV1↑, major pro-apoptotic mechanisms of capsaicin is via the vanilloid receptors, primarily TRPV1
i-Ca+2?, causing a concomitant influx of Ca2+: severe condition of mitochondria calcium overload. at high concentration (> 10 µM), capsaicin induces a slow but persistent increase in intracellular Ca2+
MMP↓, depolarization of mitochondria membrane potential
Cyt‑c↑, release of cytochrome C
Bax:Bcl2↑, activation of Bax and p53 through C-jun N-terminal kinase (JNK) activation
P53↑,
JNK↑,
PI3K↓, blocking the Pi3/Akt/mTOR signalling pathway, capsaicin increases levels of autophagic markers (LC3-II and Atg5)
Akt↓,
mTOR↓,
LC3II↑,
ATG5↑,
p62↑, enhances p62 and Fap-1 degradation and increases caspase-3 activity to induce apoptosis in human nasopharyngeal carcinoma cells
Fap1↓,
Casp3↑,
Apoptosis↑,
ROS↑, generation of ROS in human hepatoma (HepG2 cells)
MMP9↓, inhibition of MMP9 by capsaicin occurs via the suppression of AMPK-NF-κB, EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling pathway
eff↑, capsaicin 8% patch could promote the regeneration and restoration of skin nerve fibres in chemotherapy-induced peripheral neuropathy in addition to pain relief
eff↓, capsaicin has shown several unpleasant side effects, including stomach cramps, skin and gastric irritation, and burning sensation
eff↑, liposomes and micro-emulsion-based drugs have been known to significantly improve oral bioavailability and reduce the irritation of drugs
selectivity↑, In addition, these delivery systems can be surfaced-modified to perform site-directed/cell-specific drug delivery, thereby ensuring increased cell death of cancer cells while sparing non-selective normal cells
eff↑, Furthermore, owing to its antioxidant potential, capsaicin has been applied as a bioreduction and capping agent to synthesize biocompatible silver nanoparticles
ChemoSen↑, capsaicin has been combined with other anticancer therapies for more pronounced anticancer effects

5887-

CAR,

TV,

Antitumor Effects of Carvacrol and Thymol: A Systematic Review

Review,

Var,

Apoptosis↑, It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity,
TumCCA↑, accumulation of cells in the G1 phase, together with a reduction of cells in the S phase, slowing cell cycle/mitosis and provoking cell death.
TumMeta↓,
TumCP↓, antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR).
MAPK↓,
PI3K↓,
Akt↓,
mTOR↓,
eff↑, carvacrol appears to be more potent than thymol
*Inflam↓, these compounds present anti-inflammatory (Li et al., 2018; Chamanara et al., 2019) and antioxidant
*antiOx↑,
AXL↓, These effects occurred mainly through the inhibition of tyrosine kinase receptor (AXL) expression and an increase in malondialdehyde (MDA
MDA↑,
Casp3↑, caspase-3 activation and Bcl-2 inhibition
Bcl-2↓,
MMP2↓, promoted a decrease in Bcl-2, metalloproteinase-2 and -9 (MMP-2 and MMP-9), p-ERK, p-Akt, cyclin B1 levels and an increase in p-JNK, Bax levels, resulting in cell cycle arrest at the G2/M phase
MMP9↓,
p‑JNK↑,
BAX↑,
MDA↓, In respect of breast cancer, treatment with carvacrol decreases MDA-MB231 (Jamali et al., 2018; Li et al., 2021) and MCF-7 cells line viability
TRPM7↓, TRPM7 pathway is one of the suggested pharmacological mechanisms of action
MMP↓, decreased mitochondrial membrane potential, cytochrome C release, caspase activation, PARP cleavage
Cyt‑c↑,
Casp↑,
cl‑PARP↑,
ROS↑, Carvacrol also induced cytotoxicity and apoptosis (via caspase-3 and reactive oxygen species—ROS) of human oral squamous cell carcinoma (OC2 cell line)
CDK4↓, In tongue cancer (Tca-8113, SCC-25 cell lines), Dai et al. (2016) reported that carvacrol effectively inhibited cell proliferation through the negative regulation of CCND1 and CDK4 expression, and the positive regulation of p21 expression,
P21↑,
F-actin↓, A blockade of TRPM7 channels, reduced expression of MMP-2 and F-actin, was also observed, together with the inhibition of PI3K/Akt and MAPK
GSH↓, by increasing ROS, Bax, Caspase-3, -9 levels and reducing Bcl-2 and GSH levels.
*SOD↑, Moreover, carvacrol was able to increase the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH), along with a reduction of lipid peroxides and the enzymes AST, ALT, AL
*Catalase↑,
*GPx↑,
*GSR↑,
*GSH↑,
*lipid-P↓,
*AST↓,
*ALAT↓,
*ALP↓,
*LDH↓,
DNAdam↑, hepatocellular carcinoma induced by diethylnitrosamine (DEN), carvacrol treatment promoted DNA fragmentation
AFP↓, carvacrol showed a reduction in serum levels of alpha-fetoprotein (AFP), alpha l-fucosidase (AFU), vascular endothelial growth factor (VEGF
VEGF↓,
Weight↑, Carvacrol supplementation significantly improved the weight gain and growth rate of animals with colon cancer
*chemoP↑, reduction in oxidative stress damage (higher levels of GSH, GPx, GR, SOD and CAT), suggesting that carvacrol presents chemopreventive effects
ROS↑, In vitro, carvacrol and thymol increased the generation of reactive oxygen species in 24.63% (n = 17) of the studies, a fact that is also observed in chemotherapeutics

5880-

CAR,

In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis

vitro+vivo,

Lung,

A549

nude mice, present study commenced to formulate CANE by an energy intensive ultrasonication method.

in-vitro,

Nor,

BEAS-2B

in-vitro,

Lung,

PC9

Dose↝, prepare a carvacrol nanoemulsion (CANE) using an ultrasonication technique and further evaluation of its anticancer potential against human lung adenocarcinoma A549 cells. (160nm)
mt-ROS↑, The CANE induced reactive oxygen species (ROS) production in A549 cells,
p‑JNK↑, leading to activation of key regulators of apoptosis such as p-JNK, Bax and Bcl2 as well as release of cytochrome C, and activation of the caspase cascade.
BAX↑,
Cyt‑c↑,
Casp↑,
AntiTum↑, CANE displayed a strong antitumor potential in vivo using an athymic nude mice model.
ER Stress↑, Abnormally high ROS levels create ER stress with the involvement of three major signaling proteins IRE1-α, PERK and ATF-6
LDH↑, higher LDH activity, which is a well-established biomarker released by damaged cells, was observed in CANE-treated cells
selectivity↑, CANE displayed no cytotoxicity up to 100 µg/ml against normal bronchial epithelium cells (BEAS-2B)
Apoptosis↑, Induction of apoptosis and ROS production in the presence of CANE
DNAdam↑, potential role on DNA damage and chromatin condensation
IRE1↑, We observed a higher expression of IRE1-α in CANE treated cells
XBP-1↑, similar expression pattern for XBP-1
CHOP↓, down-regulation of CHOP, p-eIF2α, and GRP78 was observed in CANE-treated cells
p‑eIF2α↓,
GRP78/BiP↓,
Ca+2↑, increase of Ca+2 levels in CANE-treated cells. A 2.5 fold higher Ca+2 was observed at 100 μg/ml CANE treated cells
MMP↓, CANE severely altered mitochondrial membrane potential (Δψm) in a dose-dependent manner.
Bcl-2↓, up- and down-regulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl2) proteins
Casp3↑, higher levels of cleaved caspase-9 and caspase-3 in cells treated with CANE in a dose-dependent manner
Casp9↑,
eff↓, To confirm this, A549 cells were first treated with N-acetyl-L-cysteine NAC (5 mM), a strong scavenger of ROS, prior to CANE (100 µg/ml) treatment and observed a marked reduction in ROS generation
TumW↓, A significant (p < 0.05) 34.2 and 62.1% reduction in tumor weight was observed in the mice treated with 50 and 100 mg/Kg CANE, orally three times in a week
Weight↑, body weights of 100 mg/kg CANE treated mice remained static up to the second week and increased further up to 4 weeks
eff↑, ultrasonication consider as simple, cost-effective, clean and prompt aseptic technique16, wherein large droplets ruptured into small droplets by ultrasound leading to the formation of nano-scale droplets
eff↑, We selected polysorbate 80 as a surfactant (HLB, 15), which is regarded as safe for using in pharmaceutical and food industries1

5893-

CAR,

TV,

Thymol and Carvacrol: Molecular Mechanisms, Therapeutic Potential, and Synergy With Conventional Therapies in Cancer Management

Review,

Var,

*Inflam↓, Monoterpenes like thymol and carvacrol are recognized for their anti‐inflammatory and anticancer properties,
AntiCan↑,
PI3K↓, Thymol derivatives, such as 1,2,3‐triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression.
Akt↓,
mTOR↓,
NOTCH↓,
PIK3CA↓,
EGFR↓, thymol exhibits anti‐EGFR activity, while carvacrol modulates the HIF‐1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management.
Hif1a↓,
VEGF↓,
ChemoSen↑, Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise.
RadioS↑,
eff↝, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application.
*cardioP↑, cardioprotective (Joshi et al. 2023), neuroprotective (Forqani et al. 2023) and hepato‐nephroprotective
*neuroP↑,
*hepatoP↑,
Apoptosis↑, Induction of Apoptosis
MMP↓, The apoptosis was due to ROS production, variations in the mitochondrial membrane, caspase‐3 activation, and DNA damage
Casp3↑,
ROS↑,
DNAdam↑,
eff↑, Thymol derivative, known as compound 10 (IC50 6.17 μM) exhibited 3.2‐fold more inhibition than 5‐fluorouracil (IC50 20.09 μM) against MCF‐7
BAX↑, Carvacrol (25, 50, 75, and 90 μM) enhanced the expression of Bax, Bad, Fas‐L, and cytochrome c, activated caspase‐9/3 and caspase‐8, induced cell cycle at G0/G1
BAD↑,
FasL↑,
Cyt‑c↑,
Casp9↑,
Casp8↑,
TumCCA↑,
P21↑, improved the expression of proteins (p21, cyclin D1, CDK4), and downregulated the SMO and GLI1 proteins expression in CC
Smo↓,
Gli1↓,
JNK↑, Moreover, thymol activated JNK and p38 MAPK while impeding the ERK pathway
ERK↓,
MAPK↓, Besides thymol, carvacrol has also been reported to inhibit MAPK or ERK pathways in previous studies.
TRPM7↓, inhibited TRPM7 expression in liver fibrotic C57BL/6J mice
Wnt/(β-catenin)↓, hymol inhibited HCT116 and LoVo cell line invasion via downregulating the Wnt/β‐catenin pathway and reducing c‐Myc and Cyclin D1 expression
BioAv↝, thymol and carvacrol are volatile, and their stability is influenced by these factors (temperature, light, oxygen, and pH)
BioAv↑, Ultrasonication is an effective technique to enhance the stability of thymol and other bioactive compounds. 400 watts of power elevated the performance of NC‐CH formulations, and NC‐CH‐400 displayed increased solubility.

5943-

Cela,

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Review,

Arthritis,

Review,

IBD,

Review,

AD,

Review,

Park,

*other↝, The most abundant and promising bioactive compound derived from the root of this plant is celastrol, also called tripterine, which possess a broad range of biological activities
*other↝, TW is generally used in the treatment of Crohn’s disease (CD) in China.
*CRP↓, Inflammatory parameters, including c-reactive protein (CRP), also decreased
*eff↝, Etanercept plus TW had an equivalent therapeutic effect to that of Etanercept plus MTX and were both well tolerated
*other↑, TW in human kidney transplantation (26). Rejection occurred in 4.1% of patients treated with TW versus 24.5% of control patients, showing efficacy in the prevention of renal allograph rejection
*CXCR4↓, celastrol decreases hypoxia-induced FLS invasion by inhibiting HIF-1α-mediated CXCR4 transcription
*IL1β↓, Authors have shown that it decreases the production of IL-1β, IL-6, IL-17, IL-18, and TNF by SIC cells harvested from arthritic rats
*IL6↓,
*IL17↓,
*IL18↓,
*TNF-α↓,
*MMP9↓, celastrol reduces MMP-9 production, which limits bone damage
*PGE2↓, celastrol suppresses LPS-induced expression of PEG2 via the downregulation of COX-1 and COX-2 activation
*COX1↓,
*COX2↓,
*PI3K↓, associated with a decrease in PI3K/Akt pathway
*Akt↓,
*other↑, Remarkably, this bone-protective property of celastrol in arthritic models is further supported by studies performed in cancer models
TumCCA↑, celastrol induces cell cycle arrest, apoptosis, and autophagy by the activation of reactive oxygen species (ROS)/c-Jun N-terminal kinases (JNK) signaling pathway
Apoptosis↑,
ROS↑,
JNK↑,
TumAuto↑, celastrol is still able to induce autophagy through HIF/BNIP3 activation
Hif1a↓, The inhibitory effect of celastrol on angiogenesis is mediated by the suppression of HIF-1α,
BNIP3↝,
HSP90↓, The inhibition of HSP90 by celastrol
Fas↑, activation of Fas/Fas ligand pathway in non-small-cell lung cancer
FasL↑,
ETC↓, inhibition of mitochondrial respiratory chain (MRC) complex I
VEGF↓, This inhibition of HIF-1α leads to the decrease of its target genes, such as the VEGF
angioG↓, Angiogenesis Inhibition
RadioS↑, celastrol can overcome tumor resistance to radiotherapy in prostate (129) and lung cancer cells
*neuroP↑, celastrol is a promising neuroprotective agent in animal models of neurodegenerative diseases, such as Parkinson disease (149), Huntington disease (149–151), Alzheimer disease
*HSP70/HSPA5↑, his induction of HSP70 by celastrol explains its beneficial effects not only in neurodegenerative disorders but also in inflammatory diseases.
*ROS↓, celastrol protects human dopaminergic cells from injury and apoptosis and prevents ROS generation and mitochondrial membrane potential loss
*MMP↑,
*Cyt‑c↓, It inhibits cytochrome c release, Bax/Bcl-2 alterations, caspase-9/3 activation, and p38 MAPK activation
*Casp3↓,
*Casp9↓,
*MAPK↓,
*Dose⇅, Authors discuss that it seems to have a narrow therapeutic window, and suggest that it may have a biphasic effect with protective properties at low concentrations and toxic effects at higher concentrations.
*HSPs↑, induces a set of HSPs (HSP27, 32, and 70) in rat cerebral cortical cultures, which are selectively impacted during the progression of this disease
BioAv↓, Due to this poor water solubility, celastrol has low bioavailability. oral administration of celastrol in rats results in ineffective absorption into the systemic circulation, with an absolute bioavailability of 17.06%
Dose↝, narrow therapeutic window of dose together with the occurrence of adverse effects. Our own data showed in vivo that the doses of 2.5 and 5 μg/g/day are effective and non-toxic in the treatment of arthritis in rats;

2653-

Cela,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, It has been widely studied as chemopreventive and anticancer drug
Catalase↑,
ROS↑, ROS induction has been attributed as the primary mode through which celastrol mediates its anticancer effects.
HSP90↓, celastrol has been reported to inhibit HSP90 function
Sp1/3/4↓, induce suppressor of specificity protein (Sp) repressors [79], activate the PKCzeta–AMPK-p53–PLK 2 signaling axis [73], and activate the JNK pathway [80,81] to induce apoptosis.
AMPK↑,
P53↑,
JNK↑,
ER Stress↑, celastrol induces ER stress [78], mitochondrial dysfunction, specifically disruption of mitochondrial membrane potential [72,78,82], and cell cycle arrest at G2/M phase [76,77] and S phase [75]
MMP↓,
TumCCA↑,
TumAuto↑, Interestingly, at low concentrations (i.e., below the cytotoxic threshold) celastrol was found to induce autophagy in gastric cancer cells through ROS-mediated accumulation of hypoxia-inducible factor 1-α via the transient activation of AKT.
Hif1a↑,
Akt↑,
other↓, (1) inhibition of mitochondrial respiratory chain complex I activity [80];
Prx↓, (2) inhibition of peroxiredoxins, namely peroxiredoxin-1 [76] and peroxiredoxin-2 [78].

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↓,

1298-

CGA,

Chlorogenic acid regulates apoptosis and stem cell marker-related gene expression in A549 human lung cancer cells

in-vitro,

Lung,

A549

Bcl-2↓,
BAX↑,
Casp3↑,
p38↑,
JNK↑,
Nanog↓,
SOX2↓,
OCT4↓, POU5F1

2791-

CHr,

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

in-vitro,

Ovarian,

OV90

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

1144-

CHr,

8-bromo-7-methoxychrysin-induced apoptosis of hepatocellular carcinoma cells involves ROS and JNK

in-vitro,

HCC,

HepG2

10 μmol/L

in-vitro,

HCC,

Bel-7402

in-vitro,

Nor,

HL7702

BrMC had little effect on human embryo liver L-02 cells  ****

Casp3↑,
*ROS∅, BrMC did not affect ROS generation in L-02 cells
ROS↑,
JNK↑,
*toxicity↓, BrMC had little effect on human embryo liver L-02 cells

1571-

Cu,

Copper in cancer: From pathogenesis to therapy

Review,

NA,

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

13-

CUR,

Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action

Review,

BC,

P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

167-

CUR,

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

in-vitro,

Pca,

PC3

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

463-

CUR,

Curcumin induces autophagic cell death in human thyroid cancer cells

in-vitro,

Thyroid,

10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h

in-vitro,

Thyroid,

FTC-133

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

8505C

TumAuto↑,
LC3II↑,
Beclin-1↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↑, p-ERK1/2
p62↓,
p‑PDK1↓,
p‑Akt↓,
p‑p70S6↓,
p‑PIK3R1↓,
p‑S6↓,
p‑4E-BP1↓,

2654-

CUR,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

ROS↑, ROS induction has been implicated as one of the mechanisms of the anticancer activity of curcumin and its derivatives in various cancers
Catalase↓, Curcumin induces ROS by inhibiting the activity of various ROS-related metabolic enzymes, such as CAT, SOD1, glyoxalase 1, and NAD(P)H dehydrogenase [quinone] 1 [146,149]
SOD1↓,
GLO-I↓,
NADPH↓,
TumCCA↑, ROS accumulation further mediates G1 or G2/M cell cycle arrest [146,147,150,154], senescence [146], and apoptosis.
Apoptosis↑,
Akt↓, downregulation of AKT phosphorylation [145
ER Stress↑, endoplasmic reticulum stress (namely through the PERK–ATF4–CHOP axis)
JNK↑, activation of the JNK pathway [151],
STAT3↓, and inhibition of STAT3 [155].
BioAv↑, Additionally, the combination of curcumin and piperine, a pro-oxidative phytochemical that drastically increases the bioavailability of curcumin in humans

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↑,

4916-

DSF,

Cu,

The immunomodulatory function and antitumor effect of disulfiram: paving the way for novel cancer therapeutics

Review,

Var,

TumCP↓, inhibits proliferation, migration, and invasion of malignant tumor cells.
TumCMig↓,
TumCI↓,
eff↑, divalent copper ions can enhance the antitumor effects of DSF
Imm↑, immunomodulatory properties of DSF
ROS↑, Elevated production of reactive oxygen species (ROS) and suppression of the ROS/NF-κB signaling pathway
NF-kB↓,
chemoP↑, DSF has been shown to effectively inhibit NF-κB pathway activity and augment the apoptotic impact of 5-fluorouracil (5-FU) on colorectal cancer cells when administered in conjunction with 5-FU
JNK↑, Activate the JNK signaling pathway
FOXO↑, In acute myeloid leukemia, DSF/Cu2+ enhances the expression of the oncogene FOXO and inhibits the expression of the oncogene MYC, inducing G0/G1 cell cycle arrest and tumor cell apoptosis
Myc↑,
TumCCA↑,
Apoptosis↑,
RadioS↑, DSF/Cu2+ enhances the efficacy of conventional chemotherapy and chemoradiation, while remaining cost-effective
PD-L1↑, DSF can upregulate PD-L1 expression by promoting DNMT1-mediated hypomethylation of IRF7
eff↑, DSF was found to markedly enhance the efficacy of anti-PD-1 antibody treatment
CSCs↓, Inhibition of cancer stem cells
Dose↝, DSF's oral dosage form is ineffective for cancer treatment due to its instability in the gastric environment and rapid degradation in the body
Half-Life↑, DSF encapsulated PEG-PLGA NPs have been shown to improve tumor site delivery and prolong systemic circulation half-life.

5009-

DSF,

Cu,

Activation of Oxidative Stress and Down-Regulation of Nuclear Factor Erythroid 2-Related Factor May Be Responsible for Disulfiram/Copper Complex Induced Apoptosis in Lymphoid Malignancy Cell Lines

vitro+vivo,

lymphoma,

 (1μM) of Cu2+,

0.435±0.109μM and 0.085±0.015μM DS

AntiTum↑, Disulfiram (DS), an antialcoholism drug, demonstrates strong antitumor activity in a copper (Cu)-dependent manner.
ROS↑, DS/Cu induces reactive oxidative stress (ROS) which activates stress related signaling pathway (c-Jun-amino-terminal kinase, JNK).
JNK↑,
NRF2↓, Nrf2 expression was increased when Raji cells were treated for less than 12h and decreased after 18h or 24h treatment
eff↓, N-acetyl-L-cysteine (NAC), an antioxidant, can partially attenuate DS/Cu complex-induced apoptosis
TumCD↑, Therefore the DS/Cu induced ROS may be higher than that antioxidant factors could protect and thus the Nrf2-mediated cellular survival mechanism was disabled through down regulation of Nrf2 to allow initiation of death process.

5006-

DSF,

Cu,

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

vitro+vivo,

lymphoma,

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

642-

EGCG,

Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect

ROS↑, under high-dose conditions. Autooxidation of EGCG generates substantial ROS
H2O2↑, One EGCG molecule could produce more than two H2O2 molecules
Apoptosis↑,
Trx↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
TrxR↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
JNK↑,
HO-1↑,
Fenton↑,

Showing Research Papers: 1 to 50 of 100
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 100

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 2, GPx↑, 2, GSH↑, 3, GSR↑, 1, HDL↑, 1, HO-1↓, 1, HO-1↑, 1, Keap1↓, 1, lipid-P↓, 1, MDA↓, 2, NRF2↑, 3, ROS↓, 5, ROS∅, 1, SOD↑, 3, SOD1↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 1, MMP∅, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2, AMPK↑, 1, glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 1, LDH↓, 1, LDH↑, 1, p‑PPARγ↓, 1,

Cell Death ⓘ

Akt↓, 1, Casp3↓, 2, Casp3∅, 1, Casp9↓, 2, Cyt‑c↓, 1, Cyt‑c∅, 1, Fas↓, 1, HGF/c-Met↑, 1, iNOS↓, 1, JNK↑, 1, MAPK↓, 2,

Transcription & Epigenetics ⓘ

other↑, 2, other↝, 2,

Protein Folding & ER Stress ⓘ

CHOP↑, 2, cl‑eIF2α↑, 1, GRP78/BiP↑, 2, GRP94↑, 1, HSP70/HSPA5↑, 1, HSPs↑, 1, p‑PERK↑, 1,

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↑, 1, PI3K↓, 1,

Migration ⓘ

5LO↓, 1, MMP9↓, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 4, CRP↓, 2, CXCR4↓, 1, IL17↓, 1, IL18↓, 2, IL1β↓, 3, IL6↓, 3, IL8↓, 1, Imm↑, 1, Inflam↓, 5, NF-kB↓, 2, PGE2↓, 1, TLR4↓, 2, TNF-α↓, 4,

Protein Aggregation ⓘ

AGEs↓, 1,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

ALAT↓, 2, ALP↓, 1, AST↓, 2, CRP↓, 2, IL6↓, 3, LDH↓, 1, LDH↑, 1,

Functional Outcomes ⓘ

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

Infection & Microbiome ⓘ

AntiViral↑, 1,
Total Targets: 91

Scientific Paper Hit Count for: JNK, c-Jun N-terminal kinase (JNK)

5 Silver-NanoParticles
5 Capsaicin
5 Curcumin
5 Shikonin
5 Thymoquinone
4 Berberine
4 Copper and Cu NanoParticles
4 Piperlongumine
4 Silymarin (Milk Thistle) silibinin
3 Allicin (mainly Garlic)
3 Alpha-Lipoic-Acid
3 Apigenin (mainly Parsley)
3 Carvacrol
3 Disulfiram
3 Fisetin
3 Gambogic Acid
3 Luteolin
3 Magnetic Fields
2 Vitamin C (Ascorbic Acid)
2 Baicalein
2 brusatol
2 Thymol-Thymus vulgaris
2 Celastrol
2 Chlorogenic acid
2 Chrysin
2 Phenethyl isothiocyanate
2 Plumbagin
2 Vitamin K2
1 Camptothecin
1 Cisplatin
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Radiotherapy/Radiation
1 Betulinic acid
1 Boswellia (frankincense)
1 EGCG (Epigallocatechin Gallate)
1 Honokiol
1 HydroxyTyrosol
1 Juglone
1 Magnolol
1 Melatonin
1 Magnetic Field Rotating
1 Niclosamide (Niclocide)
1 Phenylbutyrate
1 Propolis -bee glue
1 SonoDynamic Therapy UltraSound
1 Hyperthermia
1 Parthenolide
1 salinomycin
1 Gemcitabine (Gemzar)
1 Salvia miltiorrhiza
1 Aflavin-3,3′-digallate
1 Ursolic acid

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

JNK 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 ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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