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

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?,

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/PTGS2↓, 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↓,

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/DDIT3↑,
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/DDIT3↑,
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/PTGS2↓,
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/DDIT3↑, 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/PTGS2↓,
*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/DDIT3↑, 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/CCL2↓, 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].

7180-

CHA,

Chaetocin: A review of its anticancer potentials and mechanisms

Review,

Var,

TumCG↓, . Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related
TumCP↓,
Apoptosis↑, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration.
TumCCA↑,
angioG↓,
TumCI↓,
TumCMig↓,
SUV39H↓, chaetocin inhibits the activities of histone lysine methyltransferase SUV39H1
TrxR↓, formed covalent adducts with numerous proteins, including the thioredoxin-thioredoxin reductase (Trx-TrxR) system, hypoxia inducible factor-1 alpha (HIF-1α), heat shock protein 90 (Hsp90)
Hif1a↓,
HSP90↓,
ox-Trx1↑, ↑ oxidized TRX-1 & ROS activation; ↓ PI3K/AKT pathway & p-AKT; ↑ caspase-3, caspase-8 & caspase-9 activation; ↑ cleaved PARP proteins; ↓ BCL-2, BCL-XL, MCL-1, XIAP
ROS↑,
PI3K↓,
Akt↓,
Casp3↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
XIAP↓,
DR5↑, ↑ DR5 & CHOP, ATF3;
CHOP/DDIT3↑,
ATF3↑,
angioG↓, chaetocin also indirectly targets tumour cells by inducing antiangiogenic effects in the tumour microvasculature.
VEGF↑, robust decrease in secreted VEGF in the culture media of treated cells and subsequent downregulation of the target genes of VEGFA, LDHA, ENO1 and HZF-1,
LDHA↓,
ENO1↓,

6212-

CUR,

Rad,

Radiosensitization and Radioprotection by Curcumin in Glioblastoma and Other Cancers

Review,

Var,

RadioS↑, Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent
*radioP↑, curcumin has been found to possess radioprotective properties, since it can lessen inflammatory toxicities associated with radiotherapy, like dermatitis, mucositis, and myelosuppression
EGFR↓, Curcumin can suppress the gene expression of EGFR, and downregulate the TGF-β pathway, thus leading to inhibition of cancer-associated fibroblasts (CAF)
TGF-β↓,
ROS↑, Curcumin can induce ROS generation and suppress DNA repair machinery, thus leading to increased radiation-induced cell death
P53↑, upregulation of both the expression and activity of p53, regulation of the anti-apoptotic PI3K signaling, and suppression of the activity of NF-κB and COX-2
PI3K↓,
NF-kB↓, curcumin increased radiation-induced apoptotic death primarily through inhibition of the NF-κB signaling pathway
COX2/PTGS2↓,
EMT↓, Curcumin was found to suppress radiation-induced EMT resulting in the inhibition of NSCLC migration and invasion
Hif1a↓, inhibition of the expression of both hypoxia-inducible factor 1-alpha (HIF-1a) and heat shock protein 90 (HSP90) proteins and increase in the levels of ROS
HSP90↓,
mTOR↓, In cervical cancer, curcumin has been studied as a potent mTOR inhibitor when given together with irradiation.
*Catalase↑, 40 rats were exposed to curcumin 1 day before irradiation to 3 consecutive days after irradiation, the levels of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA), were found to be considerably eleva
*SOD↑,
*MDA↑,
*Wound Healing↑, treatment with curcumin stimulated wound healing,
*hepatoP↑, curcumin treatment prior to radiation can prevent liver damages, mainly through the modulation of the NF-κB pathway and reduction of oxidative stress (upregulation of SOD, CAD and GSH levels in the curcumin-treated group)
*NF-kB↓,
*ROS↓,

6671-

Deg,

A Novel Derivative of the Natural Agent Deguelin for Cancer Chemoprevention and Therapy

in-vitro,

Nor,

BEAS-2B

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H460

HSP90↓, natural compound deguelin has promising preventive and therapeutic activity against diverse cancers by directly binding to heat-shock protein 90 (Hsp90) and thus suppressing its function.
toxicity↝, Potential side effects of deguelin over a certain dose, however, could be a substantial obstacle to its clinical use.
eff↑, One derivative, SH-14, showed several features of potential superiority for clinical use:
chemoPv↑, novel derivative SH-14 has strong potential for cancer chemoprevention and therapy, with equivalent efficacy and lesser toxicity (versus deguelin).
p53 Wildtype↓, hich leads to decreased expression of a number of Hsp90 client proteins, including mutated p53, cyclin-dependent kinase 4, mitogen-activated protein kinase (MAPK) kinase-1/2 (MEK1/2), Akt and hypoxia-inducible factor (HIF)-1α,
CDK4↓,
MAPK↓,
Hif1a↓,
selectivity↑, Deguelin has antitumor activity in vitro or in vivo at doses producing no toxic effects to normal cells or tissues and so may be a promising cancer preventive and therapeutic agent
compI↓, Researchers originally identified deguelin as a potent mitochondria complex I, NADH dehydrogenase inhibitor and implicated mitochondrial dysfunction and diminished complex I activity as factors in the pathophysiology of Parkinson’s disease (PD;
TumCP↓, Synthesis of five derivatives of deguelin that inhibit Hsp90 function and lung cancer cell proliferation
BioAv↑, SH-14 has better aqueous solubility than deguelin

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/CDKN1B↑, 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↓,

6391-

Eug,

BCP,

5-FU,

Exploring Mechanism of Actions for Eugenol and Beta-Caryophyllene to Combat Colorectal Cancer Chemotherapy Using Network Pharmacology

in-vitro,

CRC,

HCT116

eff↑, MTT assay revealed in-vitro cytotoxic effects of EUG, BCP, and 5-FU, with a noteworthy reduction in IC50 values observed when combining the compounds, indicating synergistic effects
ChemoSen↑,
HSP90↓, Molecular docking studies indicate that EUG, BCP, and 5-FU effectively inhibit the core target protein HSP90AA1
Dose↝, We aimed to lower the IC50 value of 5-FU (6 to 192.19 µM) by combining it with the three concentrations of EUG and BCP (50 µM, 100 µM, and 200 µM) to reduce its side effects
TumAuto↑, promote autophagy and inhibit apoptosis through PI3K/Akt/mTOR pathway and JNK/P38 pathway, which are key pathways in epithelial to mesenchymal transition inhibition.
Apoptosis↑,
PI3K↓,
Akt↓,
mTOR↓,
JNK↓,
p38↓,
EMT↓,

6911-

FIS,

New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells

vitro+vivo,

BC,

MMP↓, Mito-fisetin, when used at low micromolar concentrations, stimulated the dissipation of mitochondrial membrane potential and oxidative stress, and affected mitochondrial function, resulting in apoptosis induction in senescent breast cancer cells.
mt-ROS↑, Mito-Fisetin mF3 Induces Oxidative Stress in Mitochondria
Apoptosis↑,
p‑AMPK↑, Mito-fisetin-mediated cytotoxicity was due to increased levels of phosphorylated AMPK, decreased levels of AKT and HSP90,
Akt↓,
HSP90↓,
PI3K↓, Fisetin may interfere with the activity of cell survival promoting signaling pathways such as PI3K/AKT/mTOR and mitochondrial function to stimulate anticancer effects by the inhibition of cell proliferation, metastatic potential, and angiogenesis and
Akt↓,
mTOR↓,
TumCP↓,
TumMeta↓,
angioG↓,
TumCD↑,
selectivity↑, Normal cells were less sensitive to mito-fisetin treatment
TumVol↓, Mito-Fisetin mF3 Inhibits Tumor Size and Induces Cytotoxicity In Vivo

7066-

GamB,

Unravelling the Therapeutic Potential of Gambogic Acid: Deciphering Its Molecular Mechanism of Action and Emerging Role as an Anticancer Xanthone

Review,

Var,

angioG↓, anti-angiogenesis, anti-metastasis, synergistic effects and chemo-sensitization.
TumMeta↓,
ChemoSen↑, GA was reported to increase the intracellular concentration at lower doses of chemotherapeutic drug that helped develop it for combinatorial therapy to exploit its synergistic activity to selectively target cancer cells.
*cardioP↑, biological activities including anticancer, anti- cardiovascular disease (CVD) antiinflammatory, anti-viral, anti-parasitic, anti-infectiousness, antioxidant, and a promising molecule to treat osteoarthritis
*Inflam↓,
*AntiViral↑,
*antiOx↑,
NF-kB↓, suppressing NF-κB activity through modification of 179Cys of IKKβ moieties, resulting decreased expression of TNFα, COX-2, and iNOS
TNF-α↓,
COX2/PTGS2↓,
iNOS↓,
Apoptosis↑, apoptosis, autophagy and suppressing propagation and invasion of cancer cells
TumAuto↑,
TumCP↓,
TumCI↓,
BioAv↓, clinical applications are severely limited due to the poor aqueous solubility (0.013mg/mL) requiring repeat injections.
ROS↑, GA enhances production of reactive oxygen species (ROS) by collapsing the mitochondrial transmembrane potential (MMP), increasing downregulation of SIRT1 in multiple myeloma
MMP↓,
SIRT1↓,
Akt↓, GA inhibits AKT/mTOR complex 1 (mTORC1) by upregulating (AMP-activated protein kinase) AMPK and LRIG1 (leucine-rich repeats and immunoglobulinlike domains 1)
mTORC1↓,
AMPK↑,
LRIG1↑,
ER Stress↑, The inhibition of proteasomal system by GA contributes to the dilation of ER and induces ER stress and mitochondrial membrane depolarization leading to the formation of mega-mitochondria in treated cancer cells.
Paraptosis↑, GA induces paraptosis in cancer cells
Ferroptosis↑, GA induced ferroptosis in HCT116 colon cancer cells was observed
HSP90↓, GA directly inhibits the expression of HSP90, a pleiotropic regulator of multiple signalling pathways, and increases the GSH depletion leading to an increased level of LPOs and ultimately the cell undergoes ferroptosis.
GSH↓,
lipid-P↑,
GPx4↓, figure 4
miR-21↓, GA regimens also decreased the miR-21 expression and blocked PI3K/Akt signaling pathway by enhancing PTEN activity [48].
PI3K↓,
Akt↓,
PTEN↑,
ASAP2↓, GA inhibited the proliferation, migration and invasion by downregulating the expression of ASAP2 and CDK7
CDK7↓,

7067-

GamB,

Gambogic Acid and Its Role in Chronic Diseases

Review,

Var,

*NF-kB↓, GA Inhibits Signaling of Nuclear Factor-Kappa B (NF-jB)
PI3K↓, GA Inhibits Phosphatidylinositol 3′-Kinase/Protein Kinase B (PI3K/Akt)
Akt↓,
STAT3↓, table 15.1 GA Inhibits Signal Transducer and Activator of Transcription-3 (STAT-3) Pathways
STAT5↓,
IL6↓,
COX2/PTGS2↓, GA Inhibits COX-2
iNOS↓, GA Inhibits iNOS
MMPs↓,
Src↓, GA Inhibits Src
PKA↓,
CXCR4↑, GA Inhibits Chemokine X-Receptor 4 (CXCR4) and Downstream Signaling Pathways
VEGF↓,
Bcl-2↓, GA Inhibits the Expression of Bcl-2 Family Proteins
Bcl-xL↓,
IAP1↓,
Mcl-1↓,
survivin↓,
cycD1/CCND1↓, GA Inhibits Expression of Cyclin D1
HSP90↓,
HSP70/HSPA5↓,
MAPK↓, GA Inhibits Mitogen-Activated Protein Kinase (MAPK)
HATs↓, GA Inhibits CBP/p300 Histone Aceyltransferase (HAT) and Histone Deacetylase (HDAC)
HDAC↓,
FAK↓, GA Inhibits the Activation of Focal Adhesion Kinase (FAK)
ROS↑, GA Induces the Production of Reactive Oxygen Species (ROS)
MMP7↓, GA Inhibits Matrix Metalloproteinase 7 & 9 (MMP-7 & 9)
MMP9↓,
α-tubulin↑, GA Inhibits Tubulin
cl‑PARP↑, GA Induces Cleavage of Poly(ADP-Ribose) Polymerases (PARPs)
TNF-α↓, GA Inhibits Tumor Necrosis Factor-a (TNF-a)
BID↑, GA Induces BID
BAD↑, GA Induces BAD
Cyt‑c↑, GA, induces the expression of cytochrome c in colorectal cancer HT-29, bladder cancer T24 and UMUC3, breast cancer MDA-MB-231, and human hepatocellular carcinoma cells
Casp3↑, GA Induces the Activation of Caspase-3 and Caspase-9
Casp9↑,
*AntiArt↑, GA inhibits RA by inhibiting the levels of cytokines and key inflammatory molecules [
*antiPs↑, recent study showed that GA could be used as an anti-psoriatic agent

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/ABCB1↓,
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.

7213-

GAs,

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

vitro+vivo,

NPC,

CNE2

xenografted nude mice

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF7

in-vitro,

Lung,

H1975

ATPase↓, n this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 μg·mL−1
HSP90↓,
TumCP↓,
*toxicity↝, GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity.
MMP2↓, GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2).
MMP9↓,
HER2/EBBR2↓,
c-Raf↓,
Akt↓,
Bcl-2↓,
other↝, findings of this study demonstrate that GAS extracted from the seed coats of G. biloba show in vitro Hsp90 ATPase inhibitory activity and cytotoxic activity against four human cancer cell lines.

7101-

Geld,

Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs

in-vitro,

Nor,

*toxicity↑, These results suggest that hepatotoxicity exhibited by the Hsp90 inhibitors belonging to benzoquinone ansamycins could be attributed to superoxide.
*AntiBio↑, Geldanamycin (GM), a benzoquinone ansamycin antibiotic, is a natural product inhibitor of Hsp90 with potent and broad anti-cancer properties.
HSP90↓,
AntiCan↑,

7100-

Geld,

Rad,

Preferential sensitization of tumor cells to radiation by heat shock protein 90 inhibitor geldanamycin

in-vitro,

Var,

HSP90↓, The purpose of this study was to investigate the radiosensitizing effect of geldanamycin (GA), an inhibitor of heat shock protein 90, on tumour cells and normal cells.
Akt↓, combination of radiation and GA abolished Akt activities and strongly enhanced the induction of apoptosis in tumour cells which depend on Akt protein activities for cell survival.
RadioS↑, GA sensitized tumour cells to radiation in preference to normal cells.
selectivity↑,

7099-

Geld,

Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation

in-vitro,

CRC,

DLD1

RadioS↑, GA radiosensitized both cell lines, but potentiated X-ray sensitivity more in SQ-5 than in DLD-1 cells.
EF-1α↓, GA enhances the radiation sensitivity of human tumour cells by inhibiting the EGFR signal transduction system and the Akt signalling pathway.
Akt↓,
HSP90↓, Targeting Hsp90 with GA provides a promising experimental strategy for radiosensitization of carcinoma.

7098-

Geld,

Geldanamycins: Potent Hsp90 Inhibitors with Significant Potential in Cancer Therapy

Review,

Var,

HSP90↓, Geldanamycin is a potent heat shock protein inhibitor with remarkable antiproliferative activity.
*toxicity↑, However, it shows pronounced hepatotoxicity in animal models and unfavorable pharmacokinetic properties.
*toxicity↓, review discusses the mechanism of action of geldanamycin, its pharmacokinetic properties, and the various approaches employed to alleviate its toxicity and maximize its clinical efficacy.
*BioAv↑, The derivative 17-AAG retained the potent anticancer activity of geldanamycin but with reduced hepatotoxicity and improved bioavailability.its clinical development was halted due to its low water solubility and its hepatotoxicity.
eff↑, By contrast, 17-DMAG offers several advantages over 17-AAG, such as higher water solubility, better bioavailability, reduced metabolism, and greater anticancer activity.(stopped due to its higher toxicity compared to 17-AAG )
*toxicity↓, In contrast to geldanamycin and its 17-AGG and 17-DAMG analogs, gamitrinib showed no toxicity to normal cells or tissues and did not disrupt Hsp90 homeostasis
other↝, Overall, this review highlights the therapeutic potential of geldanamycin derivatives as anticancer drugs.

7097-

Geld,

Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry

Review,

Var,

HSP90↓, Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature.
*Bacteria↓, Geldanamycin (GA), a yellow colored compound first isolated from Streptomyces hygroscopicus var. geldanus in 1970 was found to possess antibacterial properties.
*toxicity↑, although GA itself has not progressed to the clinic due to unacceptable liver toxicity,

7096-

Geld,

A biochemical rationale for the anticancer effects of Hsp90 inhibitors: slow, tight binding inhibition by geldanamycin and its analogues

Study,

Var,

HSP90↓, Two analogues of the Hsp90 inhibitor geldanamycin are currently in clinical trials
AntiTum↑, The benzoquinone ansamycins are an important class of Hsp90 inhibitors that possess potent antitumor activity in preclinical models and may emerge as efficacious therapeutic agents for the treatment of cancer

7095-

Geld,

Mechanistic studies on Hsp90 inhibition by ansamycin derivatives

Study,

Var,

HSP90↓, ansamycin family of natural products and their derivatives, such as geldanamycin (GA), are well-known inhibitors of the essential ATPase activity of Hsp90
selectivity↑, they show selectivity towards tumour cells.

7250-

Gink,

Ginkgetin from Ginkgo biloba: mechanistic insights into anticancer efficacy

Review,

Var,

AntiCan↑, This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity
toxicity↓, Due to its safety and efficacy, GBLs have become one of the most widely used herbs in Europe and the United States, with annual sales of related products reaching billions of dollars
ChemoSen↑, ginkgetin synergizes with chemotherapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects.
chemoP↑, In addition to standalone use, ginkgetin has synergistic effects with other drugs by enhancing drug efficacy and alleviating side effects.
TumCCA↑, mechanisms, including inducing cell cycle arrest, triggering programmed cell death, and preventing invasion and angiogenesis.
TumCD↑,
TumCI↓,
angioG↓,
Ferroptosis↑, figure 1
Imm↑, emerging evidence suggests that ginkgetin could enhance the body’s immunity and has an anti-tumor function
MOMP↑, ginkgetin triggered the intrinsic apoptosis pathway, demonstrated by increased mitochondrial outer membrane permeabilization (MOMP) and the release of Cytochrome c into the cytoplasm,
Cyt‑c↑,
Casp↑, which activated the caspase cascade and upregulated cleaved caspase-3, caspase-9, and PARP, ultimately leading to apoptosis [
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Apoptosis↑,
ROS↑, Moreover, ginkgetin mediated the activation of caspase cascade by the intracellular reactive oxygen species generated possibly through auto-oxidation of this biflavone, leading to apoptosis in OVCAR-3 cells
TumAuto↑, Ginkgetin induced autophagic cell death in non-small cell lung cancer (NSCLC) A549 cells
GPx4↓, Ginkgetin synergized with cisplatin to increase ferroptosis in NSCLC cells, which was confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio
xCT/SLC7A11↓,
RadioS↑, Similarly, when breast cancer cells generated radioresistance, ginkgetin promoted ferroptosis in 4T1 cells after radiotherapy by suppressing the Nrf2/HO-1 axis activity, elevating intracellular levels of reactive oxygen species (ROS) and ferrous ions
NRF2↓,
HO-1↓,
HSP90↓, MD simulations showed minimal fluctuations in the binding mode between ginkgetin and Hsp90, suggesting that ginkgetin may be an effective Hsp90 inhibitor
Dose↝, The IC50 values of ginkgetin treatment ranged from 0.58 to 150 μM, which varied due to differences in cell type, treatment time, number of plated cells, and treatment method.
Dose↝, For animal experiments, the concentration of administration ranged from 10 to 100 mg/kg, owing to different types of tumors and administration methods.
BioAv↓, Consequently, improving the bioavailability and water solubility of ginkgetin is an urgent issue that needs to be addressed
BioAv↝, In addition to considering administration routes such as intraperitoneal or intravenous injection, improvements can be made through innovative dosage form design and advanced drug delivery platforms
CYP3A4↓, research has shown that ginkgetin exhibited significant inhibition activity towards CYP3A4, which is a pivotal enzyme in the metabolic processing of many commonly used drugs, and the IC50 value was evaluated as 0.106 ± 0.004 μM
*toxicity↑, Moreover, ginkgetin induced acute kidney injury in treated mice and the main pathological lesions were confirmed in the tubule, glomeruli, and interstitium injuries
*toxicity↝, ginkgetin displayed potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressing hUGT1A1), which ...plays a crucial role in the metabolic detoxification of endogenous toxicants (e.g., bilirubin) and a variety of clinical drugs

7169-

HDN-1,

CHA,

Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90

in-vitro,

Lung,

H1975

in-vitro,

Lung,

HCC827

in-vitro,

Lung,

A549

HSP90↓, These results indicate that HDN-1 and chaetocin are inhibitors of Hsp90 and that SUV39H1 is a novel client protein of Hsp90.
TumCP↓, H1975, HCC827 and A549. HDN-1 inhibited the proliferation of these cancer cell lines with an IC50 of 0.22, 0.54, and 1.06 μM,
EGFR↓, We found that HDN-1 treatment reduced the expression levels of EGFR, Stat3, Akt, and Erk, and their active phosphorylated forms and downregulated the expression of Raf and Cyclin D1
STAT3↓,
Akt↓,
ERK↓,
Raf↓,
cycD1/CCND1↓,
SUV39H↓, HDN-1 is an analogue of chaetocin (Figure 6A), which is a fungal mycotoxin with histone methyltransferase SUV39H1 inhibitory activity

7456-

HNK,

Honokiol in the treatment of triple-negative breast cancer: a network pharmacology approach and experimental validation

vitro+vivo,

BC,

MDA-MB-231

 zebrafish xenograft model.

in-vitro,

BC,

MDA-MB-468

Apoptosis↑, Results indicated that HNK induces apoptosis in MDA-MB 231 and MDA-MB 468 cells and inhibits their migration and proliferation.
TumCMig↓,
TumCP↓,
HSP90↓, HNK targets against TNBC, including HSP90AA1, AKT1, EGFR, ERBB2, HSP90AB1, PGR, MDM2, HDAC1, NR3C1, and MAPK14.
AKT1↓,
EGFR↓,
HSP90↓,
MDM2↓,
HDAC1↓,

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

7814-

ISQ,

Isoquercitrin Attenuates Steatohepatitis by Inhibition of the Activated NLRP3 Inflammasome through HSP90

in-vivo,

Nor,

 MCD-Induced Steatohepatitis Mice Model

*ROS↓, As a quercetin glycoside, isoquercitrin (IQ) has a broad inhibitory effect on oxidative stress, cancers, cardiovascular diseases, diabetes, and allergic reactions in vitro and in vivo.
*AntiCan↑,
*cardioP↑,
*AntiDiabetic↑,
*NLRP3↓, IQ inhibited the activated NLRP3 inflammasome by down-regulating the expression of heat shock protein 90 (HSP90) and suppressor of G-two allele of Skp1 (SGT1).
*HSP90↓,
*AST↓, . A lower level of serum AST and serum ALT (Figure 1G,H) in both the SIL and IQ groups further proved the protective effects of SIL and IQ on the liver.
*ALAT↓,

Showing Research Papers: 1 to 50 of 62
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 62

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1, AntiBio↑, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1, Catalase↑, 1, GSH↑, 1, MDA↑, 1, NRF2↑, 1, Prx↑, 1, ROS↓, 3, SOD↑, 1, SOD2↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1, AMPK↑, 1, p‑PPARγ↓, 1,

Cell Death(tgid=5) ⓘ

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

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 2, other↝, 2,

Protein Folding & ER Stress(tgid=8) ⓘ

HSP70/HSPA5↑, 1, HSP90↓, 1, HSPs↑, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

PI3K↓, 1,

Migration(tgid=13) ⓘ

MMP9↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX1↓, 1, COX2/PTGS2↓, 1, CRP↓, 1, CXCR4↓, 1, IL17↓, 1, IL18↓, 2, IL1β↓, 2, IL6↓, 2, IL8↓, 1, Inflam↓, 1, NF-kB↓, 2, PGE2↓, 1, TNF-α↓, 2,

Protein Aggregation(tgid=19) ⓘ

NLRP3↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1, CRP↓, 1, IL6↓, 2,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, antiPs↑, 1, cardioP↑, 3, chemoPv↑, 1, hepatoP↑, 2, neuroP↑, 1, radioP↑, 1, toxicity↓, 3, toxicity↑, 5, toxicity↝, 2, Wound Healing↑, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1, Bacteria↓, 1,
Total Targets: 67

Scientific Paper Hit Count for: HSP90, HSP90

9 Celastrol
8 Ashwagandha(Withaferin A)
7 Geldanamycin
4 Gambogic Acid
4 Honokiol
3 Quercetin
2 Apigenin (mainly Parsley)
2 chaetocin
2 Radiotherapy/Radiation
2 Deguelin
2 Luteolin
2 Magnetic Fields
1 DTS(dibenzyl trisulphide) from Anamu
1 Andrographis
1 Capsaicin
1 Carvacrol
1 hydroxychloroquine
1 Chemotherapy
1 Curcumin
1 EGCG (Epigallocatechin Gallate)
1 Eugenol
1 Beta-Caryophyllene
1 5-fluorouracil
1 Fisetin
1 Garcinol
1 Ginkgolic acids
1 Ginkgetin
1 epipolythiodioxopiperazine / epipolythiopiperazine-2,5-dione
1 isoquercitrin
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:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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