HSP70/HSPA5 Cancer Research Results

HSP70/HSPA5, heat shock proteins 70 kilodalton: Click to Expand ⟱

Source:

Type:

Also known as HSPA5
Enhanced expression of Hsp70 is associated with tumorigenesis for breast cancer, endometrial cancer, gastric cancer, and acute leukemia; with poor prognoses.
-These adenosine triphosphatases unfold misfolded or denatured proteins and can keep these proteins in an unfolded, folding-competent state. They also protect nascently translating proteins, promote the cellular or organellar transport of proteins, reduce proteotoxic protein aggregates and serve general housekeeping roles in maintaining protein homeostasis.
-HSP70 family of proteins can be thought of as a potent buffering system for cellular stress, either from extrinsic (physiological, viral and environmental) or intrinsic (replicative or oncogenic) stimuli. As such, this family serves a critical survival function in the cell. Not surprisingly, cancer cells rely heavily on this buffering system for survival. The overwhelming majority of human tumors overexpress HSP70 family members, and expression of these proteins is typically a marker for poor prognosis.
-HSP70 helps cancer cells survive under stressful conditions, such as hypoxia or nutrient deprivation, by preventing protein misfolding and aggregation. This allows cancer cells to maintain their proliferative capacity.
-Tumor Progression: Elevated levels of HSP70 have been associated with tumor progression and metastasis.

Scientific Papers found: Click to Expand⟱

2657-

AL,

Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases

Review,

CardioV,

Review,

AD,

*Inflam↓, allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others).
*antiOx↑, improving the antioxidant system
*neuroP↑,
*cardioP↑,
*AntiTum↑,
*mtDam↑, Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes.
*HSP70/HSPA5↑, llicin improves mitochondrial function by enhancing the expression of HSP70 and decreasing RAAS activation
*NRF2↑,
*RAAS↓,
*cognitive↑, Allicin enhances the cognitive function of APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice by decreasing the expression levels of Aβ, oxidative stress, and improving mitochondrial function.
*SOD↑, positive effects on cognition in an AD mouse model by administrating a preventive dose of allicin. These effects might be mediated by an increase of SOD and reduction of ROS
*ROS↓,
*NRF2↑, Chronic treatment with allicin increased the expression of NRF2 and targeted downstream of NRF2, such as NADPH, quinone oxidoreductase 1 (NQO1), and Î³-glutamyl cysteine synthetase (Î³-GCS), in the hippocampus of aged mice
*ER Stress↓, protective effects of 16 weeks of allicin treatment in a rat model of endoplasmic reticulum stress-related cognitive deficits.
*neuroP↑, allicin was able to ameliorate depressive-like behaviors by decreasing neuroinflammation, oxidative stress iron aberrant accumulation,
*memory↑, allicin improved lead acetate-caused learning and memory deficits and decreased the ROS level
*TBARS↓, Oral administration of allicin was able to reduce thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and concurrently increased (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in a rat model of
*MPO↓,
*SOD↑,
*GSH↑,
*iNOS↓, decreasing the expression of iNOS and increased the phosphorylation of endothelial NOS (eNOS)
*p‑eNOS↑,
*HO-1↑, OSCs upregulate the endogenous antioxidant NRF2 and heme oxygenase-1 (HO-1)

3345-

ART/DHA,

Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells

in-vitro,

GBM,

ROS↑, Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death
Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
lipid-P↑,
HSP70/HSPA5↑, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5)
ER Stress↑, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4)
ATF4↑,
GRP78/BiP↑, HSPA5
MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
GPx4↑, DHA induced-ER stress in turn activated cell protection against ferroptosis through PERK-ATF4- HSPA5 activation, which promoted the expression of GPX4 to detoxify peroxidized membrane lipids

1357-

Ash,

Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways

in-vitro,

GBM,

U87MG

 1.07±0.071µM

in-vitro,

GBM,

U251

0.69±0.041µM

in-vitro,

GBM,

GL26

0.23±0.015µM

mouse line

TumCP↓,
TumCCA↑, G2/M cell cycle
Akt↓,
mTOR↓,
p70S6↓,
p85S6K↓,
AMPKα↑,
TSC2↑,
HSP70/HSPA5↑,
HO-1↑,
HSF1↓,
Apoptosis↑,
ROS↑, Withaferin A elevates pro-oxidant potential in GBM cells and induces a cellular oxidative stress response
eff↓, Pre-treatment with a thiol-antioxidant protects GBM cells from the anti-proliferative and cytotoxic effects of withaferin A NAC pretreatment was able to completely prevent cell cycle shift to G2/M arrest following 1µM WA treatment at 24h

2003-

Ash,

Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells

in-vitro,

Pca,

PC3

2 μM WA

in-vitro,

Pca,

DU145

in-vitro,

Nor,

TIG-1

in-vitro,

PC,

LNCaP

TumCD↑, We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells
selectivity↑, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD)
cFos↑, WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1.
ROS↑, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts
*ROS∅, but not in normal fibroblasts
HSP70/HSPA5↑,
Apoptosis↑, WA induces apoptosis mediated by ER stress
ER Stress↑,
TumCCA↑, WA induces autophagy in breast cancer cells, but the detailed mechanism remains elusive

5175-

Ash,

Withaferin A Induces Proteasome Inhibition, Endoplasmic Reticulum Stress, the Heat Shock Response and Acquisition of Thermotolerance

in-vitro,

Cerv,

CCL-102

Inflam↓, In the present study, withaferin A (WA), a steroidal lactone with anti-inflammatory and anti-tumor properties, inhibited proteasome activity
AntiTum↑,
Proteasome↓,
ER Stress↑, and induced endoplasmic reticulum (ER) and cytoplasmic HSP accumulation in Xenopus laevis A6 kidney epithelial cells.
HSPs↑,
GRP94↑, WA induced the accumulation of HSPs including ER chaperones, BiP and GRP94, as well as cytoplasmic/nuclear HSPs, HSP70 and HSP30.
Akt↑, WA-induced an increase in the relative levels of the protein kinase, Akt,
eff↑, WA acted synergistically with mild heat shock to enhance HSP70 and HSP30 accumulation to a greater extent than the sum of both stressors individually
HSP70/HSPA5↑, WA Induced Accumulation of BiP, GRP94, HSP70 and HSP30

2685-

BBR,

Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells

in-vitro,

neuroblastoma,

CSCs↓, Berberine attenuated cancer stemness markers CD133, β-catenin, n-myc, sox2, notch2 and nestin.
CD133↓,
β-catenin/ZEB1↓,
n-MYC↓,
SOX2↓,
NOTCH2↓,
Nestin↓,
TumCCA↑, Berberine potentiated G0/G1 cell cycle arrest by inhibiting proliferation, cyclin dependent kinases and cyclins resulting in apoptosis through increased bax/bcl-2 ratio.
TumCP↓,
CDK1↓,
Cyc↓,
Apoptosis↑,
Bax:Bcl2↑,
NCAM↓, The induction of NCAM and reduction in its polysialylation indicates anti-migratory potential which is supported by down regulation of MMP-2/9.
MMP2↓,
MMP9↓,
*Smad1↑, It increased epithelial marker laminin and smad and increased Hsp70 levels also suggest its protective role.
*HSP70/HSPA5↑,
*LAMs↑,

5631-

BCA,

Perspectives Regarding the Role of Biochanin A in Humans

Review,

Var,

Review,

AD,

*BioAv↓, Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption
*Inflam↓, various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects.
AntiCan↑,
*neuroP↑, many studies have focused on the effect of BCA on neurodegenerative diseases, especially PD and AD
chemoPv↑, BCA Has Chemopreventive Activity Against Various Cancers
Dose↝, BCA is metabolized in the gut to GEN or formononetin, which is converted to daidzein and then to equol (Knight and Eden, 1996).
*SOD↑, BCA also has a gastroprotective effect through the enhancement of cellular metabolic cycles, as evidenced by increases in superoxide dismutase (SOD) and nitric oxide (NO) activity, decreases in the malondialdehyde (MDA) and Bax levels, and increases
*MDA↓,
*BAX↓,
*HSP70/HSPA5↑, and increases in Hsp70 expression
*AntiDiabetic↑, BCA is well known for its antidiabetic and hypolipidemic effects.
*Insulin↑, BCA increases the circulating insulin levels and improves insulin sensitivity, leading to body weight control, an increase in liver glycogen, and a decrease in plasma glucose
*TNF-α↓, BCA inhibits the production of inflammatory mediators, such as TNF-α, interleukin-1β (IL-1β), IL-6, iNOS, COX-2, MMP-9, and NO, in various inflammatory responses
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2↓,
*MMP9↓,
*ROS↓, BCA scavenges ROS and increases SOD activity
*PGE2↓, BCA significantly reduces the synthesis of prostaglandin E2 and/or thromboxane B2 by inhibiting COX-2 expression
*BACE↓, BCA effectively inhibits the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
*BioAv↑, Various attempts have been made to improve the solubility and bioavailability of BCA, including the use of liposomes
P-gp⇅, Interestingly, BCA has been found to stimulate P-gp in some studies (An and Morris, 2010). Therefore, the effect of BCA on P-gp may be substrate dependent.

3516-

Bor,

Boron in wound healing: a comprehensive investigation of its diverse mechanisms

Review,

Wounds,

*Inflam↓, anti-inflammatory, antimicrobial, antioxidant, and pro-proliferative effects.
*antiOx↑,
*ROS↓, The antioxidant properties of boron help protect cells from oxidative stress, a common feature of chronic wounds that can impair healing
*angioG↑, Boron compounds exhibit diverse therapeutic actions in wound healing, including antimicrobial effects, inflammation modulation, oxidative stress reduction, angiogenesis induction, and anti-fibrotic properties.
*COL1↑, Boron has been shown to increase the expression of proteins involved in wound contraction and matrix remodeling, such as collagen, alpha-smooth muscle actin, and transforming growth factor-beta1.
*α-SMA↑,
*TGF-β↑,
*BMD↑, Animals treated with boron showed favorable changes in bone density, wound healing, embryonic development, and liver metabolism
*hepatoP↑,
*TNF-α↑, BA elevates TNF-α and heat-shock proteins 70 that are related to wound healing.
*HSP70/HSPA5↑,
*SOD↑, antioxidant properties of BA showed that boron protects renal tissue from I/R injury via increasing SOD, CAT, and GSH and decreasing MDA and total oxidant status (TOS)
*Catalase↑,
*GSH↑,
*MDA↓,
*TOS↓,
*IL6↓, Boron supports gastric tissue by alleviating ROS, MDA, IL-6, TNF-α, and JAK2/STAT3 action, as well as improving AMPK activity
*JAK2↓,
*STAT3↓,
*AMPK↑,
*lipid-P↓, boron may improve wound healing by hindering lipid peroxidation and increasing the level of VEGF
*VEGF↑,
*Half-Life↝, Boron is a trace element, usually found at a concentration of 0–0.2 mg/dL in plasma with a half-life of 5–10 h, and 1–2 mg of it is needed in the daily diet

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.

1652-

CA,

Caffeic Acid and Diseases—Mechanisms of Action

Review,

Var,

Dose∅, Black chokeberries seem to be the most potent source of caffeic acid (645 mg/100 g of dry weight)
ROS⇅, Therefore, we will mention the antioxidant (and prooxidant) effects of caffeic acid only briefly
NF-kB↓, In HepG2 cells, caffeic acid (100 µM) inhibited the activity of NF-κB/IL-6/STAT3 signaling, which decreased the expression of VEGF
STAT3↓,
VEGF↓,
MMP9↓, inhibited another downstream product of NF-κB: matrix metalloproteinase 9 (MM-9), which promotes tumor invasiveness and metastases
HSP70/HSPA5↑, caffeic acid (20 μM) also decreased the expression of mortalin(mitochondrial 70 kDa heat shock protein),
AST↝, normalized levels of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol, HDL and LD
ALAT↝,
ALP↝,
Hif1a↓,
IL6↓,
IGF-1R↓,
P21↑,
iNOS↓,
ERK↓,
Snail↓,
BID↑,
BAX↑,
Casp3↑,
Casp7↑,
Casp9↑,
cycD1/CCND1↓,
Vim↓,
β-catenin/ZEB1↓,
COX2↓,
ROS↑, the chelating ability of caffeic acid is also responsible for its occasional pro-oxidant ability. After chelating Cu2+, the Cu2+ can be reduced to Cu+. combination of caffeic acid and endogenous copper ions can result in oxidative damage

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;

5944-

Cela,

HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way

in-vitro,

AML,

U937

TumCP↓, Celastrol affected the proliferation of U937 in a dose-dependent way, arresting the cell cycle at G0/G1 with 400 nM doses and triggering cell death with doses above 1000 nM.
TumCCA↑,
TumCD↑,
HSP90↓, Cell cycle arrest was accompanied by inhibition of HSP90 ATPase activity and elevation in HSP70 levels (a biochemical hallmark of HSP90 inhibition),
HSP70/HSPA5↑,
cycD1/CCND1↓, reduction in Cyclin D1, Cdk4 and Cdk6 levels
CDK4↓,
CDK6↓,
ATPase↓, celastrol's effects on ATPase activity in the protein complex pulled-down by anti-HSP90

6073-

CHL,

GEM,

Chlorophyllin exerts synergistic anti-tumor effect with gemcitabine in pancreatic cancer by inducing cuproptosis

in-vitro,

PC,

ChemoSen↑, our study introduces Chlorophyllin (CHL) as an effective therapeutic candidate to enhance the therapeutic efficacy of GEM.
eff↑, Our results demonstrate that the combination of CHL and GEM exhibits a significant synergistic anti-tumor effect by targeting multiple oncogenic processes in PC, including inhibiting cell proliferation, invasion, and migration, as well as apoptosis
AntiTum↑,
TumCP↓,
TumCI↓,
TumCMig↓,
Apoptosis↑,
GSH↓, CHL induces cuproptosis in PC cells through a multifaceted process, involving depleting cellular intracellular glutathione (GSH), increasing reactive oxygen species (ROS) levels, and subsequently upregulating the HSP70
ROS↑,
HSP70/HSPA5↑,

2807-

CHr,

Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats

in-vivo,

Nor,

Wistar rats

*antiOx↑, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic
Inflam↓,
*cardioP↑, Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways
*GSH↑, CHY at the highest dose (60 mg/kg) significantly bolstered the antioxidant status :GSH, SOD and CAT
*SOD↑,
*Catalase↑,
*GAPDH↑, significant increase in GAPDH levels was observed in CHYP group in comparison with normal group
*BAX↓, Decrease in apoptotic (Bax), increase in anti-apoptotic (Bcl-2)
*Bcl-2↑,
*PARP↓, expression of downstream signalling proteins, that is, PARP, cytochrome-C and caspase-3 were following the similar pattern. however at CHY 60 mg/kg treatment group, the levels were remarkably (P < 0·001) reduced.
*Cyt‑c↓,
*Casp3↓,
*NOX4↓, Whereas, lower levels of Nox-4 and higher levels of Nrf-2, HO-1 and HSP-70 were observed in CHYP group
*NRF2↑,
*HO-1↑,
*HSP70/HSPA5↑,

414-

CUR,

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

in-vitro,

BC,

MCF-7

114 μM

in-vitro,

BC,

MDA-MB-231

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

3712-

FA,

Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants

Review,

AD,

*antiOx↑, Ferulic acid (FA) is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger.
*Inflam↓,
*ROS↓,
*Aβ↓, “FA could prevent the development of AD, not only through scavenging reactive oxygen species, but also through direct inhibition of the deposition of fibrils in the brain”
*HO-1↑, FA plays a cytoprotective role through the up-regulation of enzymes such as heme oxygenase-1, heat shock protein 70, extracellular signal-regulated kinase (ERK) 1/2, and serine/threonine kinase (Akt).
*HSP70/HSPA5↑,
*ERK↑,
*Akt↑,
*iNOS↓, , FA inhibits the expression and/or activity of cytotoxic enzymes, including inducible nitric oxide synthase, caspases, and cyclooxygenase-2
*COX2↓,
*cardioP↑, treatment of several age-related diseases, such as neurodegenerative disorders, cardiovascular diseases, diabetes, and cancer
*memory↑, reported that the long-term administration of FA to mice protected against learning and memory deficits induced by centrally administered β-amyloid
*IL2↓, FA is able to significantly reduce the interleukin-1β (IL-1β) cortical levels
*cognitive↑, FA reversed behavioral impairment, including hyperactivity, object recognition, spatial working, and reference memory.
*APP↓, it reduced amyloidogenic APP metabolism by modulation of β-secretase, attenuated neuroinflammation, and stabilized oxidative stress.
*SOD↑, superoxide dismutase (SOD), catalase (CAT) ERK 1/2, and Akt [95].
*Catalase↑,
*Akt↑,
*BioAv↑, A good strategy to increase the bioavailability and the cytoprotective effect of compounds such as FA is the formulation of new nanoparticles.

839-

Gra,

Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway

in-vitro,

Liver,

HepG2

tumCV↓,
Apoptosis↑,
HSP70/HSPA5↑,
GRP94↑,
ER Stress↑, evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5
p‑PERK↑,
p‑eIF2α↑,
GRP78/BiP↑,
CHOP↑,

2254-

MF,

Effect of 60 Hz electromagnetic fields on the activity of hsp70 promoter: an in vivo study

in-vivo,

Nor,

80uT, 60Hz,2 h daily for 7 days

BALB/c mice

*HSP70/HSPA5↑, induction of hsp70 (heat-shock protein 70) expression by EMFs, as well as the reporter for the luciferase gene
HSP70/HSPA5↑, We previously found activation of hsp70 promoter in cultured HeLa and BMK16 cell lines

2256-

MF,

HPT,

Effects of exposure to repetitive pulsed magnetic stimulation on cell proliferation and expression of heat shock protein 70 in normal and malignant cells

in-vitro,

BC,

MCF-7

34mT, 50Hz 2-s bursts and 1-s rests.

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HBL-100

HSP70/HSPA5↑, HSP70 expression was increased by RPMS exposure under thermal stress at 40 degrees C and 42 degrees C in HBL-100 and HeLa.
HSP70/HSPA5∅, HSP70 was not affected by RPMS at 37°C (Fig. 5A).

2255-

MF,

Pulsed Electromagnetic Fields Induce Skeletal Muscle Cell Repair by Sustaining the Expression of Proteins Involved in the Response to Cellular Damage and Oxidative Stress

in-vitro,

Nor,

SkMC

1.5 mT PEMF for four hours repeated for two days

*HSP70/HSPA5↑, HSP70), which can promote muscle recovery, inhibits apoptosis and decreases inflammation in skeletal muscle, together with thioredoxin, paraoxonase, and superoxide dismutase (SOD2), which can also promote skeletal muscle regeneration following injury
*Apoptosis↓,
*Inflam↓,
*Trx↓,
*PONs↓, Paraoxonase 2 (PON2, Paraoxonase 3 (PON3) (+19% vs. controls)
*SOD2↓,
*TumCG↑, PEMF treatment enhanced muscle cell proliferation by approximately 20% both in cells grown in complete medium
*Diff↑, suggest the potential role of PEMF in the induction of muscle differentiation
*HIF2a↑, hypoxia-inducible transcription factor 2a (HIF-2a) (+40% vs. controls),
*Cyt‑c↑, Cytochrome c (+39% vs. controls)
P21↑, p21/CIP1 (+27% vs. controls)

2253-

MF,

Low-frequency pulsed electromagnetic field promotes functional recovery, reduces inflammation and oxidative stress, and enhances HSP70 expression following spinal cord injury

in-vivo,

Nor,

50 Hz frequency and 2.5 mT

spinal cord-injured rats.

*Inflam↓, LPEMFs decreased the expression of inflammatory factors, including tumor necrosis factor-α, interleukin-1β and nuclear factor-κB.
*TNF-α↓, after 2 weeks of LPEMF treatment, the expression of TNF-α and IL-1β were decreased in comparison with the SCI group
*IL1β↓,
*NF-kB↓, administration of LPEMFs significantly reduced the immunoreactivity of NF-κB in SCI rats
*iNOS↓, Additionally, LPEMFs exposure reduced the levels of inducible nitric oxide synthase and reactive oxygen species, and upregulated the expression of catalase and superoxide dismutase.
*ROS↓, LPEMFs can alleviate the oxidative stress by reducing ROS production following SCI
Catalase↑,
*SOD↑,
*HSP70/HSPA5↑, Furthermore, treatment with LPEMFs significantly enhanced the expression of HSP70 in spinal cord-injured rats
*neuroP↑, LPEMFs exhibit strong neuroprotective effects in the nervous system
*motorD↑, LPEMF exposure can promote locomotor recovery in SCI rats
*antiOx↑, protective effect of LPEMFs on oxidative stress may be attributed to the upregulation of antioxidant enzymes.

4105-

MF,

Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases

Review,

AD,

*Inflam↓, On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset.
*neuroP↑, TMS (60 Hz, 0.7 mT) applied to rats for 2 hours twice daily, can be neuroprotective
*NO↑, The growth curve of exposed bacteria was lower than the control, while field application increased NO levels
*ROS↓, A significant increase of free radical production has been observed after exposure to 50 Hz electromagnetic fields at a flux density of 1 mT to mouse macrophages
*NO↓, EMF represents a non-pharmacological inhibitor of NO and an inducer of MCP-1,
*MCP1↑,
*HSP70/HSPA5↑, Tokalov and Gutzeit (2004) showed the effect of ELF-EMF on heat shock genes and demonstrated that even a low dose of ELF-EMF (10 mT) caused an increase in HSPs, especially hsp70
*antiOx↑, Whereas most environmental electromagnetic radiations cause oxidative stress in the brain (Sahin and Gumuslu, 2007), ELF-EMF seems to have an antioxidant and neuroprotective effect
*NRF2↑, ELF-EMF induces the antioxidant pathway Nrf2, which is closely associated with its protective effect against neurotoxicity induced by 3-nitropropionic acid (3-NP)
*NF-kB↓, Selective inhibition of the NF-κB signaling pathway by ELF-EMF may be involved in the decrease of chemokine production.

4116-

MF,

Low‑frequency pulsed electromagnetic field promotes functional recovery, reduces inflammation and oxidative stress, and enhances HSP70 expression following spinal cord injury

in-vivo,

NA,

spinal cord-injured rats.

*Inflam↓, LPEMFs decreased the expression of inflammatory factors, including tumor necrosis factor-α, interleukin-1β and nuclear factor-κB.
*TNF-α↓,
*IL1β↓,
*iNOS↓, LPEMFs exposure reduced the levels of inducible nitric oxide synthase and reactive oxygen species, and upregulated the expression of catalase and superoxide dismutase.
*ROS↓,
*Catalase↑,
*SOD↑,
HSP70/HSPA5↑, treatment with LPEMFs significantly enhanced the expression of HSP70 in spinal cord-injured rats.

3469-

MF,

Pulsed Electromagnetic Fields (PEMF)—Physiological Response and Its Potential in Trauma Treatment

Review,

NA,

*eff↑, According to this analysis, pulse repetition frequencies higher than 100 Hz with magnet flux densities between 1 mT and 10 mT lead to the highest presence of a cellular response, although this may vary depending on the cell type and stage of growth
*eff↝, Also, repeated applications over a prolonged period of more than 10 days show a higher effect than shorter periods, while a prolonged acute exposure lasting more than 24 h seems to be less effective than an acute exposure with less than 24 h applicat
*other↑, release of Ca2+ ion and the direct activation of PEMF on voltage-gated calcium channels (VGCCs) is of great relevance.
Ca+2↑, PEMF stimulation also leads to similar membrane effects, resulting in a Ca2+ influx, which triggers further cellular signals
ROS↑, It has been proposed that the accumulation of ROS or oxidative stress may cause the upregulation of heat shock proteins (Hsp70, HIF-1), leading to cell damage.
HSP70/HSPA5↑,
*NOTCH↑, PEMF has been shown to increase the expressions of Notch4 and Hey1 during osteogenic differentiation of MSCs, suggesting that the Notch pathway, important in cellular fate and bone development, is activated by PEMF in stem cells
*HEY1↑,
*p38↑, PEMF-induced osteogenic differentiation MSCs, as well as the activation of p38 MAPK
*MAPK↑,

526-

MF,

Inhibition of Cancer Cell Growth by Exposure to a Specific Time-Varying Electromagnetic Field Involves T-Type Calcium Channels

in-vitro,

BC,

MDA-MB-231

Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern.

Thomas-EMF used in our experiments is a complex time-modulated pattern (25–6 HZ)

in-vitro,

BC,

MCF-7

in-vitro,

Pca,

HeLa

vitro+vivo,

Melanoma,

B16-BL6

in-vitro,

Nor,

HEK293

TumCG↓, Exposure to Thomas-EMF inhibited tumour growth in mice
Ca+2↑, exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca2+ influx
selectivity↑, but did not effect non-malignant cells
*Ca+2∅, only malignant cells showed enhanced Ca2+ uptake following exposure to Thomas-EMF.
ROS↑, EMF-dependent increases in reactive oxygen species, rapid influx of Ca2+, or activation of specific signaling pathway
HSP70/HSPA5↑, Some studies have shown increased expression of HSP70, a marker of cellular stress responses, in response to EMF exposures
AntiCan↑, These observations suggest that the Thomas-EMF could provide a potential anti-cancer therapy.

492-

MF,

Weak electromagnetic fields (50 Hz) elicit a stress response in human cells

in-vitro,

AML,

HL-60

10-140uT, 30mins

human fibroblasts

HSP70/HSPA5↑, HSP70 genes (A, B, and C), are induced by ELF-EMF

519-

MF,

Effects of 50-Hz magnetic field exposure on superoxide radical anion formation and HSP70 induction in human K562 cells

in-vitro,

AML,

K562

50-Hz sine wave; 1 h; 0.025-0.10 mT

HSP70/HSPA5↑, 2x

194-

MF,

Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke

Review,

Stroke,

*BAD↓,
*BAX↓,
*Casp3↓,
*Bcl-xL↑,
*p‑Akt↑,
*MMP9↓, EMF significantly decreased levels of IL-1β and MMP9 in the peri-infarct area at 24 h and 3rd day of the experiment
*p‑ERK↑, ERK1/2
*HIF-1↓,
*ROS↓, n a similar experiment, ELF-MF (50 Hz/1 mT) increased cell viability and decreased intracellular ROS/RNS in mesenchymal stem cells submitted to OGD conditions and 3 h ELF-MF exposure
*VEGF↑,
*Ca+2↓,
*SOD↑,
*IL2↑,
*p38↑,
*HSP70/HSPA5↑,
*Apoptosis↓, PEMF decreased apoptosis
*ROS↓, Nevertheless, in the presence of ischemia, EMF decreased NO and ROS concentrations.
*NO↓,

3249-

PBG,

Can Propolis Be a Useful Adjuvant in Brain and Neurological Disorders and Injuries? A Systematic Scoping Review of the Latest Experimental Evidence

Review,

Var,

*Inflam↓, ropolis was consistently demonstrated to reduce the expression of inflammatory and oxidative markers such as malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS)
*ROS↓,
*MDA↓,
*TNF-α↓,
*NO↓,
*iNOS↓,
*SOD↑, while increasing and maintaining antioxidant parameters, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)
*GPx↑,
*GSR↓,
*GSH↑,
*neuroP↑, neuroprotective effect of propolis was also demonstrated in terms of alleviating symptoms associated with aneurysm, ischemia, ischemia-reperfusion and traumatic brain injuries.
*IL6↓, Propolis reduced the expression of interleukin-6 (IL-6), TNF-α, matrix metalloproteinase-2 (MMP-2), MMP-9, monocyte chemotactic protein-1 (MCP-1), and iNOS
*MMP2↓,
*MMP9↓,
*MCP1↓,
*HSP70/HSPA5↑, while increasing the expression of protective proteins such as heat shock protein-70 (hsp70)
*motorD↑, significantly ameliorate the impairment of sensory–motor and other physical indices in animals subjected to these injuries
*Pain↓, Unsurprisingly, propolis was shown to be effective in attenuating symptoms of neuroinflammation, pain, and oxidative stress.
*VCAM-1↓, consistently shown to reduce inflammation markers such as vascular cell adhesion molecule-1 (VCAM-1), nuclear factor kappa B (NF-kB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK)-
*NF-kB↓,
*MAPK↓,
*JNK↓,
*IL1β↓, It also reduced the expression of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α
*AChE↓, propolis inhibited the activity of both acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner
*toxicity∅, Kalia et al. (2014) observed no cytotoxicity in organs, including the brain of normal mice fed up to 1000 mg propolis extract/ kg body weight.
cognitive↑, figure 4

3490-

RF,

Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases

Review,

AD,

Review,

Park,

*OS↑, Several short-term exposure studies have shown that REMFS increases lifespan in mice, worms, and flies.
*memory↑, An initial REMFS study prevented or reversed memory loss in Tg AD mouse model (AβPPsw) when a pulsed and modulated RF-EMF at 918 MHz with a SAR of 0.25–1.05 W/kg was applied over a 7 to 9 month period
*cognitive↑, preserved good cognitive function, whereas control Tg mice showed cognitive decline.
*memory↑, REMFS exposure for 2 months showed improved memory in the Y-maze task, although not in more complex tasks
*Aβ↓, 24–30% decrease of Aβ deposits.
*eff↑, lengthier EMF exposures of 1 h, and to a lesser extent 3–24 h, produced biological effects.
*HSF1↑, REMFS activates HSF1 and chaperone expression
*HSP70/HSPA5↑, EMF exposure also increases HSF1-heat shock element binding activity, thereby directly contributing to the activation of HSF1 and the stress-induced Hsp70

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

3663-

SFN,

Efficacy of Sulforaphane in Neurodegenerative Diseases

Review,

AD,

Review,

Park,

*antiOx↑, SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties,
*Inflam↓,
*Half-Life↝, SFN in rats reaches the plasma peak in 4 h, with an average half-life of about 2.2 h
*NRF2↑, Nrf2 expression can be regulated by SFN,
*NQO1↑, oxidoreductase 1 (NQO-1), heme oxygenase 1 (HO-1), GSH S-transferase, and thioredoxin reductase, thus counteract the oxidative stress
*HO-1↑, intracellular increase of GSH, as well as HO-1 and NQO-1 activity
*TrxR↑,
*ROS↓,
*TNF-α↓, regulating the levels of inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL) 6, IL-1β, inducible nitric oxide synthetase (iNOS), and cyclooxygenase-2 (COX-2)
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2↓,
*Aβ↓, SFN inhibited Aβ aggregation, tau hyperphosphorylation, as well as oxidative stress, evaluated through GSH and malondialdehyde (MDA) levels
*GSH↑, reduction of levels of MDA, TNF-α, and IL-1β, as well as by the increase of GSH
*cognitive↑, SFN treatment improved cognitive and locomotor deficits evaluated by Morris water maze and open field test.
*BACE↓, SFN, according to a dose-dependent mechanism, can inhibit BACE-1 and consequently Aβ aggregation
*HSP70/HSPA5↑, SFN increased the levels of co-chaperone of heat shock protein (HSP), C-terminus of HSP 70-interacting protein (CHIP)
*neuroP↑, SFN, through mechanisms that involve Nrf2 activation, can play a protective effect for counteracting the neurodegeneration that occurs in the PD
*ROS↓, SFN treatment has avoided both ROS production and membrane damage.
*BBB↑, SFN protected the integrity of BBB, as shown by tight junction proteins occludin and claudin-5 levels, as well as by the reduction in the expression levels of matrix metallopeptidase 9,
*MMP9↓,

3664-

SFN,

Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-β and Tau in a Mouse Model of Alzheimer's Disease

in-vivo,

AD,

A triple transgenic mouse model of AD (3 × Tg-AD

*CHIP↑, sulforaphane treatment increase levels of CHIP and HSP70
*HSP70/HSPA5↑,
*Aβ↓, sulforaphane treatment increase CHIP level and clear the accumulation of Aβ and tau.
*tau↓,

3658-

SFN,

Pre-Clinical Neuroprotective Evidences and Plausible Mechanisms of Sulforaphane in Alzheimer’s Disease

Review,

AD,

*NRF2↑, Sulforaphane potently induces transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated expression of detoxification, anti-oxidation
*antiOx↑,
*neuroP↑, The study on the neuroprotective effects of sulforaphane began in 2004 with studies showing the protective effects on neurons
*Aβ↓, every other day 10 mg/kg i.p. for 2 months in cortex: (1) reduced the numbers of Aβ plaques/mm2 in cerebral cortex
*BACE↓, reduced BACE1 protein expression
*NQO1↑, increased NQO1 transcript and protein expression
*IL1β↓, decreased IL-1β and TNF-α
*TNF-α↓,
*IL6↓, (1) decreased IL-1β and IL-6 (2) decreased COX-2 and iNOS (3) reduced NF-κB p-p65
*COX2↓,
*iNOS↓,
*NF-kB↓,
*NLRP3↓, reduced NLRP3 inflammasome
*Ca+2↓, decreased intracellular Ca2+ levels
*GSH↑, in brain: (1) increased GSH (2) decreased MDA
*MDA↓,
*ROS↓, (1) decreased ROS and MDA, (2) increased SOD activity
*SOD↑,
*HO-1↑, increased NQO1, HO-1
*TrxR↑, increased HO-1 and TrxR expression
*cognitive↑, ameliorated cognitive deficits
*tau↓, figure 1
*HSP70/HSPA5↑,

1050-

SK,

Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation

in-vitro,

Colon,

CT26

HSP70/HSPA5↑,
ROS↑, upregulation of Hsp70 was dependent on ROS induced by SK
PKM2↓,

2084-

TQ,

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

Review,

Var,

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

2109-

TQ,

Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro

in-vitro,

AML,

CEM

1.5 µg/mL

Apoptosis↓, TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax
Bcl-2↓,
BAX↑,
ROS↑, Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells.
HSP70/HSPA5↑,
Casp3↑,
Casp8↑,

Showing Research Papers: 1 to 37 of 37

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 37

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 8, Catalase↑, 4, GPx↑, 1, GSH↑, 6, GSR↓, 1, HO-1↑, 5, lipid-P↓, 1, MDA↓, 4, MPO↓, 1, NOX4↓, 1, NQO1↑, 2, NRF2↑, 6, ROS↓, 15, ROS∅, 1, SOD↑, 11, SOD2↓, 1, TBARS↓, 1, TOS↓, 1, Trx↓, 1, TrxR↑, 2,

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1, MMP↑, 1, mtDam↑, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, GAPDH↑, 1, PONs↓, 1,

Cell Death ⓘ

Akt↓, 1, Akt↑, 2, p‑Akt↑, 1, Apoptosis↓, 2, BAD↓, 1, BAX↓, 3, Bcl-2↑, 1, Bcl-xL↑, 1, Casp3↓, 3, Casp9↓, 1, Cyt‑c↓, 2, Cyt‑c↑, 1, HEY1↑, 1, iNOS↓, 8, JNK↓, 1, MAPK↓, 2, MAPK↑, 1, p38↑, 2,

Transcription & Epigenetics ⓘ

other↑, 3, other↝, 2,

Protein Folding & ER Stress ⓘ

ER Stress↓, 1, HSF1↑, 1, HSP70/HSPA5↑, 17, HSPs↑, 1,

DNA Damage & Repair ⓘ

PARP↓, 1,

Proliferation, Differentiation & Cell State ⓘ

CHIP↑, 1, Diff↑, 1, ERK↑, 1, p‑ERK↑, 1, NOTCH↑, 1, PI3K↓, 1, STAT3↓, 1, TumCG↑, 1,

Migration ⓘ

APP↓, 1, Ca+2↓, 2, Ca+2∅, 1, COL1↑, 1, LAMs↑, 1, MMP2↓, 1, MMP9↓, 5, Smad1↑, 1, TGF-β↑, 1, VCAM-1↓, 1, α-SMA↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1, p‑eNOS↑, 1, HIF-1↓, 1, HIF2a↑, 1, NO↓, 3, NO↑, 1, VEGF↑, 2,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 5, CRP↓, 1, CXCR4↓, 1, IL17↓, 1, IL18↓, 1, IL1β↓, 7, IL2↓, 1, IL2↑, 1, IL6↓, 6, Inflam↓, 10, JAK2↓, 1, MCP1↓, 1, MCP1↑, 1, NF-kB↓, 4, PGE2↓, 2, TNF-α↓, 7, TNF-α↑, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, tau↓, 2,

Protein Aggregation ⓘ

Aβ↓, 5, BACE↓, 3, NLRP3↓, 1,

Hormonal & Nuclear Receptors ⓘ

RAAS↓, 1,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BMD↑, 1, CRP↓, 1, IL6↓, 6,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, AntiTum↑, 1, cardioP↑, 3, chemoPv↑, 1, cognitive↑, 5, hepatoP↑, 1, memory↑, 4, motorD↑, 2, neuroP↑, 9, OS↑, 1, Pain↓, 1, toxicity∅, 1,
Total Targets: 124

Scientific Paper Hit Count for: HSP70/HSPA5, heat shock proteins 70 kilodalton

11 Magnetic Fields
3 Ashwagandha(Withaferin A)
3 Sulforaphane (mainly Broccoli)
2 Celastrol
2 Thymoquinone
1 Allicin (mainly Garlic)
1 Artemisinin
1 Berberine
1 Biochanin A
1 Boron
1 Bortezomib
1 Caffeic acid
1 Chlorophyllin
1 Gemcitabine (Gemzar)
1 Chrysin
1 Curcumin
1 Ferulic acid
1 Graviola
1 Hyperthermia
1 Propolis -bee glue
1 Radio Frequency
1 Rosmarinic acid
1 Shikonin

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

HSP70/HSPA5 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

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 ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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