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⟱

2646-

AL,

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

in-vitro,

Pca,

DU145

in-vitro,

Melanoma,

RPMI-8226

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

554-

Anamu,

Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

in-vitro,

NA,

769-P

TumCCA↑, induce G2 cell cycle arrest
HSP70/HSPA5↓,
HSP90↓,

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↓,

2705-

BBR,

Mechanism underlying berberine's effects on HSP70/TNFα under heat stress: Correlation with the TATA boxes

in-vivo,

Nor,

male ICR mice (8-10 weeks old, weighing 21-23 g)

in-vitro,

Nor,

PC12

HSP70/HSPA5↓, BBR was capable of decreasing the expression of both HSP70 and TNFα
TNF-α↓,

738-

Bor,

Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways

in-vitro,

GBM,

U251

in-vitro,

GBM,

A172

in-vitro,

Nor,

SVGp12

TumCP↓,
GPx4↓, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase‐3/7 activity.
GSH↓,
HSP70/HSPA5↓,
NRF2↓,
MDA↑,
Casp3↑,
Casp7↑,
Ferroptosis↑, Consequently, borax may induce ferroptosis in GBM cells
selectivity↑, Treating SVG cells with borax concentrations ranging from 0 to 800 μM for 24 h did not result in a significant reduction in viability compared to the control group

3791-

CA,

Caffeic Acid and Diseases—Mechanisms of Action

Review,

AD,

*memory↑, Feeding hyperinsulinemic rats with caffeic acid (30 mg/kg b.w./day) for 30 weeks significantly improved their memory and learning impairments caused by a high-fat diet
*cognitive↑, caffeic acid (100 mg/kg for two weeks) significantly improved learning deficits and increased cognitive function
*p‑tau↓, pretreatment with caffeic acid (10 μg/mL) decreased the level of phosphorylated tau protein
*ROS↓, Caffeic acid (100 mg/kg for two weeks) also suppressed oxidative stress, inflammation, NF-κB-p65 protein expression, and caspase-3 activity
*Inflam↓,
*NF-kB↓,
*Casp3↓,
*lipid-P↓, caffeic acid (50 mg/kg/day) improved cognitive functions and inhibited lipid peroxidation and nitric oxide formation in the brain
*AChE↓, Caffeic acid (12 μg/mL) inhibited acetylcholinesterase and butyrylcholinesterase activity in the brain of untreated rats in vitro
*BChE↓,
*GSK‐3β↓, improves cognitive functions, probably by inhibiting NF-κB and GSK3β signaling and acetylcholinesterase and butyrylcholinesterase activity (
*5LO↓, we consider the inhibitory effect of caffeic acid on 5-lipoxygenase as another factor in protecting the brain against damage
*BDNF↓, Caffeic acid also increased the expression of brain-derived neurotrophic factor (BDNF) in stressed mice; the effect was mediated by 5-lipoxygenase inhibition
VEGF↓, the primary way how caffeic acid affects hepatocellular carcinoma in vitro is inhibiting VEGF expression
HSP70/HSPA5↓, affeic acid (20 μM) also decreased the expression of mortalin(mitochondrial 70 kDa heat shock protein),

2016-

CAP,

Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin)

HSP90↓, Here, we investigated the mechanism by which capsaicin inhibits Hsp90
ATPase↓, capsaicin binds to the N-terminus of Hsp90 and inhibits its ATPase activity
eff↑, Combined treatments of capsaicin and the Hsp90 inhibitor 17-AAG improved the anti-tumor efficacy of 17-AAG in cell culture
HSP70/HSPA5↓, capsaicin triggers the lysosomal degradation of Hsp70 in various cancer cell lines
other↝, The mechanism by which capsaicin induces apoptosis in cancer cells is not well understood, but it appears to be independent of the TRPV1 receptor as neither capsazepine, a TRPV1 antagonist, nor intracellular Ca2+ chelators have been found to inhibit
NF-kB↓, capsaicin can block the activity of many oncogenic signaling proteins including NF-κB, ER, EGFR/HER2, CDK4, Src, VEGF, and PI3K/Akt, among others.
EGFR↓,
CDK4↓,
Src↓,
VEGF↓,
PI3K↓,
Akt↓,

467-

CUR,

Curcumin inhibits liver cancer by inhibiting DAMP molecule HSP70 and TLR4 signaling

in-vitro,

Liver,

HepG2

20, 50, 80 and 100 μM, 24, 48 and 72 h

TumCP↓,
TumCI↓,
TumMeta↓,
Apoptosis↑,
HSP70/HSPA5↓,
e-HSP70/HSPA5↓,
TLR4↓,

4685-

EGCG,

Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

in-vitro,

NPC,

TW01

in-vitro,

NPC,

TW06

CSCs↓, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.
EMT↓,
TumCMig↓, Inhibition on NPC sphere-derived cell colony formation, migration, and invasion by EGCG
TumCI↓,
OCT4↓, EGCG inhibited the expression of Klf-4 and Oct-4 in sphere-derived cells.
Snail↓, EGCG significantly inhibited the levels of Snail, Vimentin and increased E-Cadherin expression in a dose-dependent manner
Vim↓,
E-cadherin↓,
HSP70/HSPA5↓, EGCG suppresses the expression of HSP70 and HSP90, and exhibits anti-tumor activity in vitro and in vivo
HSP90↓,
AntiTum↓,

2857-

FIS,

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

Review,

Var,

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

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

2825-

FIS,

Exploring the molecular targets of dietary flavonoid fisetin in cancer

Review,

Var,

*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
*p‑cMyc↑,
*NRF2↑,
*GSH↑,
*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
PI3K↓,
Akt↓,
TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
p27↑,
JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
MMP2↓,
MMP9↓,
uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
cFos↓,
cJun↓,
E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
Vim↓,
N-cadherin↓,
EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
Cyt‑c↑,
Diablo↑,
Casp↑,
cl‑PARP↑,
P53↑, fisetin with induction of p53 protein
COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
PGE2↓,
HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
HSP27↓,
DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
Casp3↑,
Casp9↑,
ROS↑, This was associated with production of intracellular ROS
AMPK↑, Fisetin induced AMPK signaling
NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
Ca+2↑,
mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
p70S6↓,
ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
IRE1↑,
ATF4↑,
GRP78/BiP↑,
eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h.

2531-

M-Blu,

Anticancer activity of methylene blue via inhibition of heat shock protein 70

in-vitro,

Lung,

A549

2.5uM

in-vivo,

NA,

mice

tumCV↓, MB demonstrated lower cell viability versus NB
HSP70/HSPA5↓, In vivo, MB significantly inhibited Hsp70
LDH↓, MB significantly alleviated tumor biomarkers (ADA and LDH)
SOD↑, MB treatment significantly increased mean ± SD superoxide dismutase ([SOD

524-

MF,

Inhibition of Angiogenesis Mediated by Extremely Low-Frequency Magnetic Fields (ELF-MFs)

vitro+vivo,

PC,

MS-1

2mT, 50Hz

mouse cell line injected in mice

vitro+vivo,

PC,

HUVECs

other↓, reduction of hemangioma size, of blood-filled spaces, and in hemorrhage.
TumCP↓,
TumCMig↓,
VEGFR2↓,
TumVol↓, 20mm compared to 32mm
HSP70/HSPA5↓, HSP70 and HSP90 expression after 72 h of exposure to MF in MS-1 cells seemed markedly reduced.
HSP90↓,
TumCCA↑, (2 mT) induced cell cycle arrest but not apoptosis. “transient” arrest of MF-treated cells in G2/M phase
angioG↓, in vitro

493-

MF,

Extremely low-frequency electromagnetic field induces acetylation of heat shock proteins and enhances protein folding

in-vitro,

NA,

HEK293

10uT, 3h

in-vitro,

Liver,

AML12

mouse source

ATP↑,
HSP70/HSPA5↓, however, acetylations of HSP70 and HSP90 were increased
HSP90↓, however, acetylations of HSP70 and HSP90 were increased

94-

QC,

HPT,

Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells

in-vitro,

Pca,

LNCaP

 12.5, 25, 50, 100 umol/L

in-vitro,

Pca,

PC3

in-vitro,

Pca,

JCA-1

HSP70/HSPA5↓, Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells.
TumCCA↑,
TumCG↓, Quercetin inhibited the growth of JCA-1 and LNcap cells at concentrations over 12.5 mmol/L.
eff↑, the presence of quercetin during heating enhances the growth-inhibitory effect of heat by inducing apoptosis in the JCA-1 and LNcap cells.

3343-

QC,

Quercetin, a Flavonoid with Great Pharmacological Capacity

Review,

Var,

Review,

AD,

Review,

Arthritis,

*antiOx↑, Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC),which act as reducing agents by chelating transition-metal ions.
*ROS↓, Quercetin is a potent scavenger of reactive oxygen species (ROS), protecting the organism against oxidative stress
*angioG↓,
*Inflam↓, anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis;
*BioAv↓, It is known that the bioavailability of quercetin is usually relatively low (0.17–7 μg/mL), less than 10% of what is consumed, due to its poor water solubility (hydrophobicity), chemical stability, and absorption profile.
*Half-Life↑, their slow elimination since their half-life ranges from 11 to 48 h, which could favor their accumulation in plasma after repeated intakes
*GSH↑, Animal and cell studies have demonstrated that quercetin induces the synthesis of GSH
*SOD↑, increase in the expression of superoxide dismutase (SOD), catalase (CAT), and GSH with quercetin pretreatment
*Catalase↑,
*Nrf1↑, quercetin accomplishes this process involves increasing the activity of the nuclear factor erythroid 2-related factor 2 (NRF2), enhancing its binding to the ARE, reducing its degradation
*BP↓, quercetin has been shown to inhibit ACE activity, reducing blood pressure
*cardioP↑, quercetin has positive effects on cardiovascular diseases
*IL10↓, Under the influence of quercetin, the levels of interleukin 10 (IL-10), IL-1β, and TNF-α were reduced.
*TNF-α↓,
*Aβ↓, quercetin’s ability to modulate the enzyme activity in clearing amyloid-beta (Aβ) plaques, a hallmark of AD pathology.
*GSK‐3β↓, quercetin can inhibit the activity of glycogen synthase kinase 3β,
*tau↓, thus reducing tau aggregation and neurofibrillary tangles in the brain
*neuroP↑,
*Pain↓, quercetin reduces pain and inflammation associated with arthritis
*COX2↓, quercetin included the inhibition of oxidative stress, production of cytokines such as cyclooxygenase-2 (COX-2) and proteoglycan degradation, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1)
*NRF2↑,
*HO-1↑,
*IL1β↓, Mechanisms included decreased levels of TNF-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 (MCP-1)
*IL17↓,
*MCP1↓,
PKCδ↓, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity.
ERK↓, 50 µM resulted in the blockade of the extracellular signal-regulated kinases (ERK1/2) pathway
BAX↓, higher doses (75–100 µM) were used, as these doses reduced the expression of proapoptotic factors such as Bcl-2-associated X protein (Bax) and caspases 3 and 9
cMyc↓, induce apoptosis at concentrations of 80 µM and also causes a downregulation of cellular myelocytomatosis (c-myc) and Kirsten RAt sarcoma (K-ras) oncogenes
KRAS↓,
ROS↓, compound’s antioxidative effect changes entirely to a prooxidant effect at high concentrations, which induces selective cytotoxicity
selectivity↑, On the other hand, when noncancerous cells are exposed to quercetin, it exerts cytoprotective effects;
tumCV↓, decrease cell viability in human glioma cultures of the U-118 MG cell line as well as an increase in death by apoptosis and cell arrest at the G2 checkpoint of the cell cycle.
Apoptosis↑,
TumCCA↑,
eff↑, quercetin combined with doxorubicin can induce multinucleation of invasive tumor cells, downregulate P-glycoprotein (P-gp) expression, increase cell sensitivity to doxorubicin,
P-gp↓,
eff↑, resveratrol, quercetin, and catechin can effectively block the cell cycle and reduce cell proliferation in vivo
eff↑, cotreatment with epigallocatechin gallate (EGCG) inhibited catechol-O-methyltransferase (COMT) activity, decreasing COMT protein content and thereby arresting the cell cycle of PC-3 human prostate cancer cells
eff↑, synergistic treatment of tamoxifen and quercetin was also able to inhibit prostate tumor formation by regulating angiogenesis
eff↑, coadministration of 2.5 μM of EGCG, genistein, and quercetin suppressed the cell proliferation of a prostate cancer cell line (CWR22Rv1) by controlling androgen receptor and NAD (P)H: quinone oxidoreductase 1 (NQO1) expression
CycB/CCNB1↓, It can also downregulate cyclin B1 and cyclin-dependent kinase-1 (CDK-1),
CDK1↓,
CDK4↓, quercetin causes a decrease in cyclins D1/Cdk4 and E/Cdk2 and an increase in p21 in vascular smooth muscle cells
CDK2↓,
TOP2↓, quercetin is known to be a potent inhibitor of topoisomerase II (TopoII), a cell cycle-associated enzyme necessary for DNA replication
Cyt‑c↑, quercetin can induce apoptosis (cell death) through caspase-3 and caspase-9 activation, cytochrome c release, and poly ADP ribose polymerase (PARP) cleavage
cl‑PARP↑,
MMP↓, quercetin induces the loss of mitochondrial membrane potential, leading to the activation of the caspase cascade and cleavage of PARP.
HSP70/HSPA5↓, apoptotic effects of quercetin may result from the inhibition of HSP kinases, followed by the downregulation of HSP-70 and HSP-90 protein expression
HSP90↓,
MDM2↓, (MDM2), an onco-protein that promotes p53 destruction, can be inhibited by quercetin
RAS↓, quercetin can prevent Ras proteins from being expressed. In one study, quercetin was found to inhibit the expression of Harvey rat sarcoma (H-Ras), K-Ras, and neuroblastoma rat sarcoma (N-Ras) in human breast cancer cells,
eff↑, there was a substantial difference in EMT markers such as vimentin, N-cadherin, Snail, Slug, Twist, and E-cadherin protein expression in response to AuNPs-Qu-5, inhibiting the migration and invasion of MCF-7 and MDA-MB cells

3369-

QC,

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects

Review,

Pca,

FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

1726-

SFN,

Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential

Review,

Var,

Dose↝, Most clinical trials utilize doses of GFN ranging from 25 to 800 μmol , translating to about 65–2105 g raw broccoli or 3/4 to 23 cups of raw broccoli.
eff↝, SFN-rich powders have been made by drying out broccoli sprout
IL1β↓,
IL6↓,
IL12↓,
TNF-α↓,
COX2↓,
CXCR4↓,
MPO↓,
HSP70/HSPA5↓,
HSP90↓,
VCAM-1↓,
IKKα↓,
NF-kB↓,
HO-1↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Diablo↑,
CHOP↑,
survivin↓,
XIAP↓,
p38↑,
Fas↑,
PUMA↑,
VEGF↓,
Hif1a↓,
Twist↓,
Zeb1↓,
Vim↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Snail↓,
CD44↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDK4↓,
CDK6↓,
p50↓,
P53↑,
P21↑,
GSH↑,
SOD↑,
GSTs↑,
mTOR↓,
Akt↓,
PI3K↓,
β-catenin/ZEB1↓,
IGF-1↓,
cMyc↓,
CSCs↓, Inhibited TS-induced, CSC-like properties

2091-

TQ,

Determination of anti-cancer effects of Nigella sativa seed oil on MCF7 breast and AGS gastric cancer cells

in-vitro,

BC,

MCF-7

in-vitro,

GC,

AGS

Dose↝, The doses of 100 and 200 µg/mL were shown to be the most effective on both cancer cells
Casp3↑, N. sativa oil extract increased caspase-3 levels in both cell lines at higher concentrations and suppressed BCL2/Bax levels
Bcl-2↓,
MMP2↓, N. sativa caused a significant decrease in the expression of MMP2-9 and HSP60-70 genes over time, particularly at a dosage of 200 µg/mL compared to the control group
MMP9↓,
HSP70/HSPA5↓,

Showing Research Papers: 1 to 20 of 20

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 20

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 1, antiOx↑, 2, Catalase↑, 1, GSH↑, 2, HO-1↑, 2, lipid-P↓, 1, Nrf1↑, 1, NRF2↑, 3, ROS↓, 2, SOD↑, 1,

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,

Cell Death ⓘ

Casp3↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1, GSK‐3β↓, 2,

Migration ⓘ

5LO↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL10↓, 1, IL17↓, 1, IL1β↓, 1, Inflam↓, 3, MCP1↓, 1, NF-kB↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, BChE↓, 1, BDNF↓, 1, tau↓, 1, p‑tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, Half-Life↑, 1,

Clinical Biomarkers ⓘ

BP↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, cognitive↑, 1, memory↑, 1, neuroP↑, 2, Pain↓, 1,
Total Targets: 38

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

3 Fisetin
3 Quercetin
2 Magnetic Fields
1 Allicin (mainly Garlic)
1 dibenzyl trisulphide(DTS) from Anamu
1 Artemisinin
1 Berberine
1 Boron
1 Caffeic acid
1 Capsaicin
1 Curcumin
1 EGCG (Epigallocatechin Gallate)
1 Methylene blue
1 Hyperthermia
1 Sulforaphane (mainly Broccoli)
1 Thymoquinone

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:148  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HSP70/HSPA5 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 ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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