HSP90 Cancer Research Results

HSP90, HSP90: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a critical role in the proper folding, stabilization, and function of many proteins, including those involved in cell signaling, cell cycle regulation, and stress responses.
-Hsp90 interacts with a variety of client proteins that are often mutated or overexpressed in cancer. These include oncogenes (like HER2, BRAF, and AKT) and tumor suppressor proteins (like p53).
-Hsp90 is often overexpressed in cancer cells, which can help them survive under stressful conditions, such as those found in the tumor microenvironment. This overexpression is associated with poor prognosis in several types of cancer.
-HSPs, particularly HSP90, are known to stabilize many proteins that drive cancer progression (oncoproteins).

Scientific Papers found: Click to Expand⟱

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↓,

1352-

And,

Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy

in-vitro,

AML,

K562

Apoptosis↑, induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine
ROS↑,
HSP90↓, involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins

1547-

Api,

Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading

Review,

NA,

angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

175-

Api,

Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT

vitro+vivo,

CRC,

SW480

 40 uM for 48 hrs

vitro+vivo,

CRC,

DLD1

vitro+vivo,

CRC,

LS174T

MMP↓,
p‑Akt↓,
TumCP↓, Apigenin inhibits cell proliferation and invasion
TumCI↓,
NADH↓, down-regulated proteins by apigenin included NADH dehydrogenase [ubiquinone] iron-sulphur protein 3, heat shock protein HSP 90-alpha, stress-70 protein and NADH dehydrogenase
HSP90↓,
other↑, whereas the up-regulated proteins include Transgelin, Ras-related protein Rab-3D and 28S ribosomal protein S22
talin?,

5395-

Ash,

Withaferin A Targets Heat Shock Protein 90 in Pancreatic Cancer Cells

vitro+vivo,

PC,

PANC1

1.24uM

in-vitro,

PC,

MIA PaCa-2

2.93 uM

TumCP↓, Withaferin A exhibited potent antiproliferative activity against pancreatic cancer cells in vitro
HSP90↓, WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor)
Akt↓,
CDK4↓,
TumCG↓, WA (3, 6 mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively.
Apoptosis↑, Withaferin A induces apoptosis in pancreatic cancer cells
AntiCan↑, Withaferin A exhibits anticancer activity in pancreatic cancer xenografts

5398-

Ash,

HSP90%2C196381%2C0%2C2.html">Withaferin-A inhibits colorectal cancer growth and metastasis by targeting the HSP90/HIF-1α/EMT axis

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

SW48

TumCG↓, WA inhibits CRC’s growth, migration, and invasion by inhibiting the HSP90/HIF-1α/EMT axis.
TumCMig↓,
TumCI↓,
HSP90↓,
Hif1a↓,
EMT↓,

3155-

Ash,

Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera

Review,

Var,

Half-Life↝, The pharmacokinetic study demonstrates that a dose of 4 mg/kg in mice results in 2 Î¼M concentration in plasma (with a half-life of 1.3 h, in the breast cancer model of mice),
Inflam↓, WA has many biological activities: anti-inflammatory (Dubey et al. 2018), immunomodulatory (Davis and Girija 2000), antistress (Singh et al. 2016), antioxidant (Sumathi et al. 2007) and anti-angiogenesis
antiOx↓,
angioG↓,
ROS↑, WA induces oxidative stress (ROS) determining mitochondrial dysfunction as well as apoptosis in leukaemia cells
BAX↑, withaferin mediates apoptosis by ROS generation and activation of Bax/Bak.
Bak↑,
E6↓, The results of the study show that withaferin treatment downregulates the HPV E6 and E7 oncoprotein and induces accumulation of p53 result in the activation of various apoptotic markers (e.g. Bcl2, Bax, caspase-3 and cleaved PARP).
E7↓,
P53↑,
Casp3↑,
cl‑PARP↑,
STAT3↓, WA treatment also decreases the level of STAT3
eff↑, This study concludes that combination of DOX with WA can reduce the doses and side effects of the treatment which gives valuable possibilities for future research.
HSP90↓, by inhibiting the HSP90
TGF-β↓, WA inhibited TGFÎ²1 and TNFÎ±- induced EMT;
TNF-α↓,
EMT↑,
mTOR↓, by downregulation of mTOR/STAT3 signalling.
NOTCH1↓, WA showed inhibition of pro-survival signalling markers (Notch1, pAKT and NFÎºB)
p‑Akt↓,
NF-kB↓,
Dose↝, WA dose escalation sets consisted of 72, 108, 144 and 216 mg, fractioned in 2-4 doses/day.

3156-

Ash,

Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Review,

Var,

MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 Â± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2ârelated factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

3166-

Ash,

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives

Review,

Var,

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

3162-

Ash,

Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A

Review,

Var,

lipid-P↓, Oral cancer 20 mg/Kg ↓Lipid peroxidation : ↑SOD, glutathione peroxidase, p53, Bcl-2
SOD↑,
GPx↑,
P53↑,
Bcl-2↑,
E6↓, Cervival cancer 8mg/Kg ↓E6, E7: ↑p53, pRb, Cyclin B1, P34 Cdc2, p21, PCNA
E7↓,
pRB↑,
CycB/CCNB1↑,
CDC2↑,
P21↑,
PCNA↓,
ALDH1A1↓, Mammary cancer 0-1 mg/mouse (5-10) ↓Mammosphere number, ALDH1 activity. Vimentin, glycolysis
Vim↓,
Glycolysis↓,
cMyc↓, Mesotheliome cancer 5 mg/Kg ↓Proteasomal chymotrypsin, C-Myc : ↑ Bax, CARP-1
BAX↑,
NF-kB↓,
Casp3↑, caspase-3 activation
CHOP↑, WA is found to increase activation of Elk1 and CHOP (CCAAT-enhancer-binding protein homologous protein) by RSK, as well as up-regulation of DR5 by selectively suppressing pathway ERK
DR5↑,
ERK↓,
Wnt↓, WA inhibits Wnt/Î²-catenin pathway via suppression of AKT signalling, which inhibits cancer cell motility and sensitises for cell death
β-catenin/ZEB1↓,
Akt↓,
HSP90↓, WA-dependent inhibition of heat shock protein (HSP) chaperone functions. WA inhibits the activity of HSP90-mediated function

1358-

Ash,

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms

Review,

Var,

TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

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↓,

5905-

CAR,

HCQ,

Synergistic inhibition of metastatic melanoma by carvacrol and chloroquine: an in vitro and in silico investigation of apoptosis and molecular targets

in-vitro,

Melanoma,

eff↑, While carvacrol monotherapy exhibited weak cytotoxicity, its combination with non-toxic concentrations of chloroquine resulted in a potent and synergistic reduction in WM9 cell viability
tumCV↑,
IGF-1R↓, both carvacrol and chloroquine bind with high affinity to common molecular targets, including Insulin-Like Growth Factor 1 Receptor and Sirtuin-2.
SIRT2↓, CV and CQ may function as novel SIRT2 inhibitors
HSP90↓, Finally, our analysis confirmed that CQ, but not CV, strongly interacts with HSP90, a key chaperone protein that is frequently overexpressed in cancer
TumCP↓, Crucially, combining the two agents produced a powerful antiproliferative effect.
Akt↓, carvacrol has been shown to inhibit Akt activation in other cancer types [

5939-

Cela,

Chemo,

Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells

in-vitro,

Melanoma,

U266

in-vitro,

Melanoma,

RPMI-8226

TumCP↓, Celastrol inhibited the proliferation of MM cell lines regardless of whether they were sensitive or resistant to bortezomib and other conventional chemotherapeutic drugs.
ChemoSen↑, It also synergistically enhanced the apoptotic effects of thalidomide and bortezomib.
cycD1/CCND1↓, down-regulation of various proliferative and anti-apoptotic gene products including cyclin D1, Bcl-2, Bcl-xL, survivin, XIAP and Mcl-1.
Bcl-2↓,
survivin↓, Bcl-2, Bcl-xL, XIAP and survivin (BIRC5) were decreased with Hsp90 inhibition
XIAP↓,
Mcl-1↓,
NF-kB↓, suppression of constitutively active NF-κB
IL6↓, Celastrol also inhibited both the constitutive and IL6-induced activation of STAT3
STAT3↓,
Apoptosis↑, which induced apoptosis as indicated by an increase in the accumulation of cells in the sub-G1 phase, an increase in the expression of pro-apoptotic proteins and activation of caspase-3
TumCCA↑,
Casp3↑,
HSP90↓, Predictive analysis of HSP90 activity knock-down along with HO-1 induction
HO-1↑,
JAK2↓, Active phosphorylated STAT3, JAK2 and Src were all show reduced
Src↓,
Akt↑, Celastrol suppresses Akt activation and inhibits the expression of anti-apoptotic proteins in MM cells

5938-

Cela,

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Review,

Var,

AntiCan↑, xhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc.
BioAv↓, However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application.
Apoptosis↑, i) induced apoptosis and autophagy
TumAuto↑,
TumCCA↑, ii) cell cycle arrest
TumMeta↓, iii) antimetastatic and anti-angiogenic actions
angioG↓,
Inflam↓, iv) anti-inflammatory effects
antiOx↑, Ⅴ) antioxidant activities
ChemoSen↑, For a rational design to achieve optimal efficacy and reduce their toxicity, combination strategies used are essential
HSP90↓, celastrol not only induced the expected ubiquitinylation and degradation of ErbB2 and other HSP90 client proteins, but it also increased the levels of ROS
ROS↑,
RadioS↑, celastrol may be considered an effective radiosensitizer acting as an inhibitor of Hsp90 and a p53 activator.
P53↑,
NLRP3↓, Lee et al. introduce celastrol, as an inhibitor of NLRP3 infammasome,

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

5945-

Cela,

Targeting the dynamic HSP90 complex in cancer

Review,

Var,

HSP90↓, However, recent molecular docking studies predict that the natural product celastrol, although not uniquely an HSP90 inhibitor, disrupts the interaction of HSP90 with its co-chaperone CDC37, and destabilizes several HSP90 client kinases

5948-

Cela,

Recent Trends in anti-tumor mechanisms and molecular targets of celastrol

TumCP↓, mechanism of action of celastrol in terms of inhibition of cell proliferation and regulation of the cell cycle, regulation of apoptosis and autophagy, inhibition of cell invasion and metastasis, anti-inflammation, regulation of immunotherapy, and an
TumCCA↑,
Apoptosis↑,
TumAuto↑,
TumCI↓,
TumMeta↓,
Imm↝,
angioG↓,
Cyt‑c↑, release of cytochrome c (CytC)
ROS↑, increasing ROS levels, and activating the mitochondrial apoptosis pathway
BAX↑, upregulating the expression of CytC and the pro-apoptotic protein Bax, activating caspase-3 and caspase-9, and leading to the cleavage of PARP
Casp3↑,
Casp9↑,
cl‑PARP↑,
PrxII↓, binds to peroxiredoxin-2 (Prdx2) and inhibits its enzyme activity,
ER Stress↑, resulting in ROS-dependent endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells
mtDam↑,
CHOP↑, celastrol upregulates the expression of CHOP, Bip, XBP1s, and IRE1 proteins,
Inflam↓, Anti-inflammatory properties of celastrol
NF-kB↓, Celastrol additionally obstructed NF-κB and its downstream gene products, such as CXCR4 and MMP9, and reduced serum IL-6 and TNF-α levels to inhibit cell invasion and migration in vivo
CXCR4↓,
MMP9↓,
IL6↓,
TNF-α↓,
HSP90↓, accumulation may be due to the inhibition of HSP90 and the stress response
neuroP↑, Our mass spectrometry research also showed that celastrol directly binds to HSP90 and HSP70, exerting antitumor and neuroprotective effects
STAT3↓, Celastrol exerts anti-tumor activity by inhibiting STAT3
Prx↓, celastrol binds directly to Prdx1, Prdx2, Prdx4, and Prdx6 via active cysteine sites, inhibiting their antioxidant activity without affecting protein expression
HO-1↑, Celastrol also targeted heme oxygenase-1 (HO-1), increasing its expression in activated hematopoietic stem cells
eff↑, Research has indicated that celastrol, combined with 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), inhibits the toxic stress response of HSP90-targeted proteins, reduces the sensitization of human glioblastomas to celastrol treatment, an
eff↑, celastrol, when combined with EGFR tyrosine kinase inhibitors (EGFR-TKIs), effectively inhibits the growth and invasion of T790M mutant human lung cancer H1975
BioAv↑, nano-delivery systems present a novel pathway for the development and clinical application of celastrol, potentially overcoming existing limitations and maximizing its therapeutic potential.
toxicity↑, several significant challenges, including its pronounced hepatic and renal toxicity and potential for causing immunosuppression
CardioT↑, celastrol, which includes hepatotoxicity, cardiotoxicity, infertility toxicity, hematopoietic system toxicity and nephrotoxicity.
hepatoP↓,

5950-

Cela,

Anticancer Inhibitors of Hsp90 Function: Beyond the Usual Suspects

Review,

Var,

ChemoSen↑, and sensitizes drug-resistant cancer cells to combination therapy
HSP90↓, celastrol disrupts the association between Hsp90 and Cdc37, which leads to the degradation of Hsp90-dependent client kinases, such as Akt and Cdk4
Akt↓,
CDK4↓,

5951-

Cela,

Celastrol Suppresses Tumor Cell Growth through Targeting an AR-ERG-NF-κB Pathway in TMPRSS2/ERG Fusion Gene Expressing Prostate Cancer

vitro+vivo,

Pca,

treat mice bearing subcutaneous VCaP xenograft tumors.

NF-kB↓, Celastrol is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa cell growth.
AR↓, targeting three critical signaling pathways: AR, ERG and NF-kB in these cells
MCP1↓, Celastrol can Inhibit CCL2 Expression at Both the RNA and Protein Level
Akt↓, Multiple molecular targets of Celastrol have been identified including AKT, Hsp90 and others
HSP90↓,
TumCG↓, Studies have shown Celastrol can inhibit PCa tumor growth in vivo

2653-

Cela,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

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

1442-

Deg,

Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention

Review,

Var,

PI3K/Akt↓, Deguelin is a well-known PI3K/Akt inhibitor
IKKα↓,
AMP↓,
mTOR↓,
survivin↓,
NF-kB↓,
Apoptosis↑,
TumCCA↑, G1-S phase cell cycle arrest
toxicity↓, No sign of overt toxicity has been observed at the dose of 2–4 mg/kg
HSP90↓,
Casp↑, caspase cascade of apoptosis is initiated
TumCG↓,
p27↑, found to regulate cell cycle in colon cancer cells by stimulating p27
cycE/CCNE↓,
angioG↓,
Hif1a↓,
VEGF↓,
*toxicity↑, Treatment with deguelin, a potential mitochondria complex I inhibitor (34), reduced tyrosine hydroxylase-positive neurons, leading to Parkinson’s disease (PD).

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↓,

5152-

GamB,

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Review,

Var,

AntiCan↑, GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumCI↓,
TumMeta↓,
angioG↓,
eff↑, In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers
NF-kB↓, GA could inhibit the activation of NF-κB
P53↑, GA increases p53 expression via down-regulating MDM2 in wild type p53 expressing human cancer cells (non-small cell lung H1299)
P21↑, GA could enhance p21Waf1/CIP1 expression to induce cell apoptosis in human breast cancer cells (MCF-7) via suppressing MDM2
MDM2↓,
HSP90↓, GA was considered as a natural product inhibitor of Hsp90
Bcl-2↓, bcl-2 reduction is associated with the release of cytochrome c, leading to an apoptosis cascade reaction
Cyt‑c↑,
Casp↑,
MMP↓, rapid mitochondrial membrane depolarization and fragmentation
Casp3↑, activation of caspase-3, 9 and cleaved PARP and increased ratio of bax/bcl-2.
Casp9↑,
cl‑PARP↑,
Bax:Bcl2↑,
ROS↑, GA-induced reactive oxygen species (ROS) may be the cause of the collapse of mitochondrial transmembrane potential, which could also down-regulate SIRT1 in multiple myeloma
SIRT1↓,
TrxR1↓, GA may also interact with the thioredoxin reductase 1 (TrxR1) to elicit oxidative stress leading to ROS accumulation in hepatocellular carcinoma
Fas↓, GA with increased death receptor (Fas, FasL, Fas-associated protein with death domain (FADD) and Apaf-1) and deoxyribonucleic acid (DNA) fragmentation.
FasL↑,
FADD↑,
APAF1↑,
DNAdam↑,
NF-kB↓, GA could inhibit NF-κB pathway through suppressing IκBα and p65 phosphorylation
STAT3↓, GA also suppressed the signal transducer and activator of transcription (STAT3) phosphorylation to induce cell apoptosis
MAPK↓, GA induced cell apoptosis via suppression of mitogen-activated protein kinases (MAPK) pathway and c-fos
cFos↓,
EGFR↓, GA could also enhance epidermal growth factor receptor (EGFR) degradation and inhibit AKT/mTOR complex 1 (mTORC1) via up-regulating AMP-activated protein kinase (AMPK)-
Akt↓,
mTOR↓,
AMPK↑,
TumCCA↑, GA could obviously induce G2/M or G0/G1 arrest in various cancer cell lines, such as MCF-7 cells, K562 cells, U2OS cells, and so on
ChemoSen↑, GA distinctly sensitized doxorubicin (DOX)-resistant breast cancer cells through inhibiting P-glycoprotein and suppressing the survivin expression revealed by ROS-mediated activation of the p38 MAPK
P-gp↓,
survivin↓,

5148-

GamB,

Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics

Review,

Var,

AntiCan↑, In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent.
angioG↓, anti-angiogenesis, and chemo-/radiation sensitizer activities
ChemoSen↑, Moreover, GA has shown chemotherapy/radiation sensitization properties in different types of cancers
RadioS↑,
VEGF↓, Figure 2
MMP2↓,
MMP9↓,
Telomerase↓,
TrxR↓,
ERK↓,
HSP90↓,
ROS↑,
SIRT1↑,
survivin↓,
cFLIP↓,
Casp3↑,
Casp8↑,
Casp9↑,
BAD↓,
BID↓,
Bcl-2↓,
BAX↑,
STAT3↓,
hTERT/TERT↓,
NF-kB↓,
Myc↓,
Hif1a↓,
FOXD3↑,
BioAv↓, Unfortunately, the aqueous solubility of GA (0.013 mg/mL) is very low, thus limiting its clinical application.
BioAv↑, For example, GA can be coupled with alkanolamines to improve aqueous solubility and achieve equivalent anti-proliferation effects
P53↑, This inhibition was co-related with increase of p53 levels and reduced bcl-2 levels
eff↓, Such effect was received for GA due to production of ROS which can be removed by N-acetyl-L-cysteine (NAC, a ROS inhibitor)
OCR↓, GA exhibited a dose-dependent generation of intracellular ROS levels and lowered the oxygen consumption rate and the mitochondrial membrane potential.
MMP↓,
PI3K↓, GA happens to promote antimetastasis properties in melanoma cells by active inhibition of PI3K/Akt and ERK signaling pathways
Akt↓,
BBB↑, This study demonstrated successful uptake of GA through blood-brain barrier (BBB)
TumCG↓, GA-based nanomedicine is efficient in targeting tumors, capable to inhibit tumor growth, metastasis, angiogenesis, and reverse drug resistance
TumMeta↓,
BioAv↑, deliver GA using nanoparticles for enhanced solubility, bioavailability, adsorption and tumor imaging and targeting

809-

GAR,

High-Throughput Screen of Natural Product Libraries for Hsp90 Inhibitors

Review,

NA,

4uM

IC50 MCF7

HRI↓, inhibited the maturation of HRI
HSP90↓, This result further supports the hypothesis that physiological effects of these four compounds on cells are mediated, at least in part, through their ability to inhibit Hsp90.

2874-

HNK,

Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9

in-vitro,

Lung,

H1299

0-10uM

MMP9↓, Honokiol‐inhibited MMP‐9 expression was through promoting MMP‐9 protein degradation rather than suppressing transcription mechanism
α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl‐α‐tubulin, was accumulated after honokiol incubation.
TumCI↓, honokiol‐suppressed MMP‐9 expression and invasion ability of H1299 lung cancer cells
HDAC6↓, Honokiol‐suppressed MMP‐9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway
HSP90↓,
TumCMig↓, Honokiol inhibited lung cancer cell migration and invasion
EGFR↓, Honokiol has been verified to inhibit the EGFR‐mediated signaling pathwa

2876-

HNK,

Honokiol from Magnolia spp. induces G1 arrest via disruption of EGFR stability through repressing HDAC6 deacetylated Hsp90 function in lung cancer cells

in-vitro,

Lung,

A549

0, 5, 10, 15, 20 and 40 µM) for 24, 48, and 72 h.

23.55 ± 1.18 µM

in-vitro,

Lung,

H23

in-vitro,

Lung,

HCC827

EGFR↓, Honokiol down-regulated EGFR expression was through ubiquitin/proteasome degradation.
HSP90↓, Honokiol repressed Hsp90 and EGFR association and followed by EGFR degradation.

2878-

HNK,

Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6-mediated matrix metalloproteinase 9

in-vitro,

Lung,

H1299

TumCMig↓, migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment.
TumCI↓,
MMP9↓, proteolytic activity of MMP-9, rather than MMP-2, was inhibited in honokiol-treated H1299 cells.
α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl-α-tubulin, was accumulated after honokiol incubation
HDAC6↓, suppression of migration and invasion activities by honokiol was through inhibiting HDAC6-mediated Hsp90/MMP-9 interaction and followed by MMP-9 degradation in lung cancer.
HSP90↓, Honokiol-suppressed MMP-9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway

1243-

LA,

Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line

in-vitro,

BC,

MDA-MB-231

Hif1a↓, LRS
HSP90↓, LRS
GLUT1↓, LRS, SLC2A1 (GLUT1)
VHL↓, LCS
SHARP↑, LCS

2925-

LT,

Luteolin Induces Carcinoma Cell Apoptosis through Binding Hsp90 to Suppress Constitutive Activation of STAT3

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HEK293

in-vitro,

BC,

MCF-7

HSP90↓, This study indicated that luteolin may act as a potent HSP90 inhibitor in antitumor strategies.
p‑STAT3↓, luteolin induced a notable reduction in the level of Tyr705-phosphorylated STAT3,
Apoptosis↑, Luteolin Induces Apoptosis of Cancer Cells
selectivity↑, cytotoxicity to cancer cells including HeLa and HepG2, but showed a very slight cytotoxicity to normal cells, such as WRL-68, HEK293 and XJH cells

2924-

LT,

Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1

in-vitro,

GC,

in-vivo,

NA,

p‑STAT3↓, treatment of luteolin in these GC cells significantly inhibited STAT3 phosphorylation and reduced the expression of STAT3 targeting gene Mcl-1, Survivin and Bcl-xl
STAT3↓,
Mcl-1↓,
survivin↓,
Bcl-xL↓,
HSP90↓, t luteolin could bind to HSP-90 directly, and decrease STAT3 phosphorylation

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

3847-

MSM,

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement

Review,

Arthritis,

*Inflam↓, common use as an anti-inflammatory agent
*Pain↓, A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity.
*ROS↓,
*antiOx↑,
*Dose↝, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects
*Half-Life↝, Pharmacokinetic studies indicate that MSM is rapidly absorbed in rats [63,64] and humans [65], taking 2.1 h and <1 h, respectively.
*NF-kB↓, The inhibitory effect of MSM on NF-κB results in the downregulation of mRNA for interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) in vitro
*IL1↓,
*IL6↓,
*TNF-α↓,
*iNOS↓, MSM can also diminish the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through suppression of NF-κB;
*COX2↓,
*NLRP3↓, MSM negatively affects the expression of the NLRP3 inflammasome by downregulating the NF-κB production of the NLRP3 inflammasome transcript and/or by blocking the activation signal in the form of mitochondrial generated reactive oxygen species (ROS)
*NRF2↑, MSM influences the activation of at least four types of transcription factors: NF-κB, signal transducers and activators of transcription (STAT), p53, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2).
*STAT↓, MSM has been shown to repress the expression or activities of STAT transcription factors in a number of cancer cell lines in vitro
*Cartilage↑, , in vitro studies suggest that MSM protects cartilage through its suppressive effects on IL-1β and TNF-α
*eff↑, Supplementation with glucosamine, chondroitin sulfate, MSM, guava leaf extract, and Vitamin D improved physical function in patients with knee osteoarthritis based on the Japanese Knee OA Measure
*eff↑, MSM in combination with boswellic acid was also shown to improve knee joint function as assessed through the Lequesne Index
*GSH↑, MSM is able to restore the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio to normal levels, decrease NO production, and reduce neuronal ROS production following HIV-1 Tat exposure
*uricA↓, Humans studies show promise for MSM as an antioxidant with similar results noted, including reductions in MDA [19,167,168], protein carbonyls (PC) [167,168], and uric acid [168] and increases in GSH [167] and TEAC [159,161,168].
tumCV↓, MSM independently has been shown to be cytotoxic to cancer cells by inhibiting cell viability through the induction of cell cycle arrest [119,122,123], necrosis [119], or apoptosis
TumCCA↑,
necrosis↑,
Apoptosis↑,
VEGF↓, reduced expression of oncogenic proteins such as vascular endothelial growth factor (VEGF) [99,100,101,123], heat shock protein (HSP)90α [100], and insulin-like growth factor-1 receptor (IGF-1R)
HSP90↓,
IGF-1?,

2396-

PACs,

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

in-vitro,

HCC,

HCCLM3

80.59 μM

in-vitro,

HCC,

SMMC-7721 cell

76.32 μM

in-vitro,

HCC,

Bel-7402

in-vitro,

HCC,

HUH7

in-vitro,

HCC,

HepG2

in-vitro,

Nor,

L02

TumCP↓, PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro.
TumCCA↓,
Apoptosis↑,
GlucoseCon↓, PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.
lactateProd↓,
PKM2↓,
Glycolysis↓, to suppress aerobic glycolysis
HK2↓, PB2 suppressed the expression of HK2, PFKFB3, and PKM2, while enhancing the expression of OXPHOS in both HCC-LM3 and SMMC-7721 cells
PFK↓,
OXPHOS↑, PB2 inhibited aerobic glycolysis and improved OXPHOS in HCC cell lines
ChemoSen↑, PB2 enhanced the chemosensitivity of SORA on HCC, both in vivo and in vitro
HSP90↓, PB2 reduced the expressions of both HSP90 and HIF-1α in a dose-dependent manner in HCC cells
Hif1a↓,

5163-

PLB,

Plumbagin suppresses epithelial to mesenchymal transition and stemness via inhibiting Nrf2-mediated signaling pathway in human tongue squamous cell carcinoma cells

in-vitro,

SCC,

SCC25

TumCP↓, PLB inhibited cell proliferation, activated death receptor-mediated apoptotic pathway,
NRF2↓, PLB induces intracellular ROS generation and regulates redox homeostasis via suppressing Nrf2-mediated oxidative signaling pathway in SCC25 cells
TumCCA↑, PLB markedly induced cell cycle arrest at G2/M phase and extrinsic apoptosis
EMT↓, and inhibited epithelial to mesenchymal transition (EMT) and stemness in SCC25 cells.
CSCs↓,
eff↓, Of note, N-acetyl-l-cysteine (NAC) and l-glutathione (GSH) abolished the effects of PLB on cell cycle arrest, apoptosis induction, EMT inhibition, and stemness a
ROS↑, PLB on ROS generation-related molecules
CycB/CCNB1↓, PLB induces G2/M arrest in SCC25 cells via downregulation of cyclin B1, CDK1/cdc2, and cdc25
CDK1↓,
CDK2↓,
CDC25↓,
Vim↓, PLB inhibited the expression of vimentin in a concentration- and time-dependent manner
OCT4↓, PLB significantly decreased the expression level of Oct-4, Sox-2, Nanog, and Bmi-1.
SOX2↓,
Nanog↓,
BMI1↓,
NQO1↓, The expression levels of NQO1, GST, and HSP90 were all markedly decreased
GSTA1↓,
HSP90↓,
toxicity↓, PLB exhibits anticancer activities with minimal side effect in vitro and in vivo,

73-

QC,

The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90

in-vitro,

Pca,

LNCaP

5, 10, 25, 50, 100 uM

 Normal prostate epithelial cells

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

HSP90↓, quercetin down-regulates the expression of Hsp90 which, in turn, induces inhibition of growth and cell death in prostate cancer cells
Casp3↑, quercetin increased caspase-3 and caspase-9 activities in both LNCaP and PC-3 cells, whereas dihydroquercetin had no effect on caspases
Casp9↑,
TumCG↓,
TumCD↑,
selectivity↑, while exerting no quantifiable effect on normal prostate epithelial cells.
toxicity↓, quercetin at doses of 40–1,900 mg/kg/day in rats showed no signs of toxicity or death

76-

QC,

Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy

in-vitro,

Pca,

PC3

 100, 150 uM

aSmase↝, Figure 3b shows that quercetin treatment caused a dose-dependent augmentation in mRNA levels of Diablo and FAS
Diablo↑,
Fas↓,
Hsc70↓, coupled with a dose-responsive reduction in transcriptional activity of HSC70, HIF1A, Mcl-1, Hsp90 and BIRC4.
Hif1a↓,
Mcl-1↓,
HSP90↓,
FLT4↓, A dose-dependent drop in mRNA levels of FLT4, EPHB4, DNAPK, PARP1, ATM, perlecan, GnTV and heparanase genes was observed after treatment of PC-3 cells with quercetin
EphB4↓,
DNA-PK↓,
PARP1↓,
ATM↓,
XIAP↝,
PLC↓,
GnT-V↝,
heparanase↝,
NM23↑, quercetin significantly exerted a dose-responsive rise in transcriptional levels of NM23 and CSR1 genes
CSR1↑,
SPP1↓, coupled with an expressive lowering in mRNA levels of SPP1, DNMT1, HDAC4, CXCR4, b-catenin and NHE1.
DNMT1↓,
HDAC4↓,
CXCR4↓,
β-catenin/ZEB1↓,
FBXW7↝,
AMACR↓,
cycD1/CCND1↓,
IGF-1R↓, down-regulation of mRNA levels of AMACR, cyclin D1, NOS2A, IGF1R, IMPDH1, IMPDH2 and HEC1
IMPDH1↓,
IMPDH2↓,
HEC1↓,
NHE1↓,
NOS2↓,

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

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

Showing Research Papers: 1 to 43 of 43

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 43

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 1, GSH↑, 3, HO-1↑, 1, Nrf1↑, 1, NRF2↑, 3, Prx↑, 1, ROS↓, 3, SOD↑, 1, SOD2↑, 1, uricA↓, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, p‑PPARγ↓, 1,

Cell Death ⓘ

Akt↓, 1, Casp3?, 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↑, 1,

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1, PI3K↓, 1, STAT↓, 1,

Migration ⓘ

Cartilage↑, 1, MMP9↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 3, CRP↓, 1, CXCR4↓, 1, IL1↓, 1, IL10↓, 1, IL17↓, 2, IL18↓, 2, IL1β↓, 3, IL6↓, 3, IL8↓, 1, Inflam↓, 2, MCP1↓, 1, NF-kB↓, 1, PGE2↓, 1, TNF-α↓, 4,

Synaptic & Neurotransmission ⓘ

tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1, NLRP3↓, 1,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BP↓, 1, CRP↓, 1, IL6↓, 3,

Functional Outcomes ⓘ

cardioP↑, 2, chemoPv↑, 1, hepatoP↑, 1, neuroP↑, 2, Pain↓, 2, toxicity↓, 1, toxicity↑, 1,
Total Targets: 69

Scientific Paper Hit Count for: HSP90, HSP90

9 Celastrol
8 Ashwagandha(Withaferin A)
3 Honokiol
3 Quercetin
2 Apigenin (mainly Parsley)
2 Gambogic Acid
2 Luteolin
2 Magnetic Fields
1 dibenzyl trisulphide(DTS) from Anamu
1 Andrographis
1 Capsaicin
1 Carvacrol
1 hydroxychloroquine
1 Chemotherapy
1 Deguelin
1 EGCG (Epigallocatechin Gallate)
1 Garcinol
1 Lactobacillus
1 Methylsulfonylmethane
1 Proanthocyanidins
1 Plumbagin
1 Sulforaphane (mainly Broccoli)

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#:149  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HSP90 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 ⓘ

Cellular Microenvironment ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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