HSPs Cancer Research Results

HSPs, Heat shock proteins: Click to Expand ⟱
Source:
Type:
Heat shock proteins (HSPs) are a diverse group of molecular chaperones that assist in proper protein folding, stabilization of proteins against aggregation, and protein trafficking. In cancer, HSPs are often overexpressed, which can help tumor cells survive the stressful conditions present in the tumor microenvironment (such as hypoxia, oxidative stress, and nutrient deprivation).

-Overexpression: Many cancers exhibit high levels of HSPs compared to their normal tissue counterparts. Overexpression of chaperones like HSP27, HSP70, and HSP90 is common in various tumors.
Scientific Papers found: Click to Expand⟱
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

5943- Cela,    Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases
- Review, Arthritis, NA - Review, IBD, NA - Review, AD, NA - Review, Park, NA
*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;

4159- dietSTF,  2DG,  CRMs,    Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms
- Review, AD, NA
*BDNF↑, enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins
*HSPs↑,
*eff↑, DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic

5055- Ex,    Why exercise has a crucial role in cancer prevention, risk reduction and improved outcomes
- Review, Var, NA
OS↑, In 2008, a cohort study of breast cancer survivors identified that patients who consistently exercised for greater than 2.5 hours per week following diagnosis had a greater than 60% reduction in the risk of all deaths compared with patients who were
IGF-1↓, Table 1, IGF1 Decreased levels, IGFBP3 Increased levels
IGFBP3↑,
BRCA1↑, BRCA1 Increased expression
BRCA2↑, BRCA2 Increased expression
RAS↓, RAS family oncogenes Suppressed activity
P53↑, P53 Enhanced activity
HSPs↑, Heat shock proteins Enhanced activity
Leptin↓, Leptin Reduced activity
Irisin↓, Irisin Enhanced activity
Resistin↓, Resistin Reduced activity
NK cell↑, NK cells Enhanced activity
CRP↓, C-reactive protein, interleukin-6, TNFα Reduced activity
IL6↓,
TNF-α↓,
PGE1↓, Prostaglandins Reduced activity
COX2↓, Cox-2 Reduced activity
*GSH↑, Glutathione, Catalase and Superoxide dismutase Increased activity
*Catalase↑,
*SOD↑,
*monoA↑, Monoamines Higher levels
*EndoR↑, Endorphins Increased release
*testos↑, testosterone increases immediately after vigorous exercise in some but not all studies. lasting for 20–60 minutes post-exercise
ROS↑, Physical activity, especially if strenuous, produces reactive oxidative species (ROS)
QoL↑, Adverse cancer-related symptoms, which have been shown to be alleviated by exercise, include fatigue, muscle weakness, thromboembolism, weight gain, loss of bone density, quality of life (QOL), psychological distress, incontinence and sexual dysfunct
BMD↑, the rate of decline in BMD was significantly less in the resistance exercise group, with a greater benefit seen in the aerobic exercise group
BowelM↑, Exercise reduces bowel transit time and ameliorates constipation and its associated abdominal cramps

2252- MF,  HPT,    Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?
- Review, NA, NA
HSPs∅, In some studies, no HSP-related effects were detected after ELF-MF exposure ranging from a few μT to mT and from minutes to 24 h, using different cell types such as astroglial cells (30), HL-60, H9c2, and Girardi heart cells (31, 32), and human kerat
*HSPs↑, exposure has also caused changes in HSP levels in a number of primary or non-transformed (“primary like”) cell lines.
eff↝, The hypothesis that non-stressed cells or organisms are quite responsive to HSP induction after ELF-MF exposure is strengthened by some in vivo studies in invertebrates
*eff↑, ELF-MF Exposure Potentiates the Effects of Heat on HSP Induction
eff↑, Interestingly, when HeLa and HL-60 cancer cells were subjected to comparable magnetic flux densities (10–140 µT), exposure durations (20–30 min) and concurrently heat stressed at 43°C, a stronger HSP70 expression was attained in coexposed cells
eff↓, An interesting finding is that MF exposure provides protection against heat-induced effects such as apoptosis, cell cycle disturbances, or proliferation inhibition in both cell models and in organisms

3457- MF,    Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis
- Review, Var, NA
Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

4199- SFN,    Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders
- Review, AD, NA - Review, Park, NA
*BBB↑, SF is able to cross the blood–brain barrier as well as to protect it
*BDNF↑, SF can protect against neuronal cell death by inhibiting apoptosis, by upregulating brain-derived neurotrophic factor (BDNF) it can enhance neuronal function and plasticity, and support neurogenesis.
*neuroG↑,
*NRF2↑, , Nrf2 inducers like SF that have no direct redox activity are often referred to as “indirect antioxidants”
*HO-1↑, (NQO1) (HO-1 or HMOX), as well as (Cat), (SOD), (Prx), (HSP), glutathione S-transferases (GST), thioredoxin reductase (Trx), glutathione synthetase (GS), glutathione peroxidases (GPx) and glutathione reductase in the brain
*Catalase↑,
*SOD↑,
*HSPs↑, It enhances the expression of HSP70, HSP90, and HSP40 in normal human fibroblasts
*GSTs↑,
*Trx↑,
*GPx↑,
*GSR↑,
*GSH↑, ability of SF to upregulate GSH in the brain is critical for antioxidant protection in youth but may become even more important with age.
*NQO1↑, SF administration to astrocytes increased NQO1 concentrations and protected against oxygen and glucose-induced astrocyte cell death
*GutMicro↑, the fact that SF modulates microbiome composition
*Inflam↓, reduces inflammation and enhances gut barrier integrity,
*neuroP↑, The effect of SF on the gut microbiome may also affect the production of short-chain fatty acids (SCFA) like butyrate, which have neuroprotective effects

3309- SIL,    Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives
- Review, NA, NA
*ROS↓, (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut.
*IronCh↑,
*MMP↑, (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance.
*NRF2↑, (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation
*Inflam↓, (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases.
*hepatoP↑,
*HSPs↑, (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins
*Trx↑,
*SIRT2↑, increased expression of protective molecules (GSH, Thioredoxins, heat shock proteins (HSPs), sirtuins, etc.)
*GSH↑,
*ROS↑, Similarly, production of O2− and NO in isolated rat Kupffer cells were inhibited by silibinin in a dose-dependent manner, with IC50 80 μM
*NADPH↓, It also decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue.
*iNOS↓,
*NF-kB↓,
*BioAv↓, active free silibinin concentration in plasma after oral consumption of SM, depending on dose of supplementation, could be in the range 0.2–2.0 μM.
*Dose↝, healthy volunteers, after an oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL
*BioAv↑, For example, silibinin concentration in the gut could reach 800 μM


Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,   ROS↑, 3,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

ETC↓, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↑, 2,   Fas↑, 1,   FasL↑, 1,   JNK↑, 2,   MAPK↑, 1,   p38↑, 1,   Proteasome↓, 1,  

Transcription & Epigenetics ⓘ

BowelM↑, 1,   other↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,   GRP94↑, 1,   HSP70/HSPA5↑, 1,   HSP90↓, 1,   HSPs↑, 3,   HSPs∅, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↝, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   BRCA2↑, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1↓, 1,   IGFBP3↑, 1,   PI3K↓, 1,   RAS↓, 1,  

Migration ⓘ

Ca+2↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL6↓, 1,   Inflam↓, 1,   NK cell↑, 1,   PGE1↓, 1,   Resistin↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

Irisin↓, 1,   Leptin↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↓, 2,   eff↑, 4,   eff↝, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

BMD↑, 1,   BRCA1↑, 1,   CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   OS↑, 1,   QoL↑, 1,  
Total Targets: 59

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 3,   GPx↑, 1,   GPx1↑, 1,   GPx4↑, 1,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 1,   HO-1↑, 1,   NQO1↑, 1,   NRF2↑, 3,   ROS↓, 2,   ROS↑, 1,   SOD↑, 2,   SOD1↑, 1,   Trx↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 2,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,   SIRT2↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   iNOS↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,   other↝, 2,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,   HSPs↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

neuroG↑, 1,   PI3K↓, 1,  

Migration ⓘ

MMP9↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 1,   CRP↓, 1,   CXCR4↓, 1,   IL17↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 2,   EndoR↑, 1,   monoA↑, 1,  

Hormonal & Nuclear Receptors ⓘ

testos↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   Dose⇅, 1,   Dose↝, 1,   eff↑, 2,   eff↝, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   neuroP↑, 2,   toxicity?, 1,  
Total Targets: 61

Scientific Paper Hit Count for: HSPs, Heat shock proteins
2 Magnetic Fields
1 Ashwagandha(Withaferin A)
1 Celastrol
1 diet Short Term Fasting
1 2-DeoxyGlucose
1 Calorie Restriction Mimetics
1 Exercise
1 Hyperthermia
1 Sulforaphane (mainly Broccoli)
1 Silymarin (Milk Thistle) silibinin
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

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