mTORC1 Cancer Research Results
mTORC1, mammalian target of rapamycin complex 1: Click to Expand ⟱
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Crucial signaling node that integrates environmental cues to regulate cell survival, proliferation, and metabolism, and is often deregulated in human cancer.
Activation of mTOR signaling is associated with oncogenic cellular processes, making mTOR a promising target for treating multiple hallmarks of the cancer phenotype.
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Scientific Papers found: Click to Expand⟱
mTORC1↓, Dihydroartemisinin (DHA), an anti-malarial drug, has been shown to possess potent anticancer activity, partly by inhibiting the mammalian target of rapamycin (mTOR) complex 1 (mTORC1)
AMPK↑, DHA activated AMP-activated protein kinase (AMPK).
TumCG↓, treatment with artesunate, a prodrug of DHA, dose-dependently inhibited tumor growth and concurrently activated AMPK and suppressed mTORC1 in RMS xenografts.
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in-vitro, |
Melanoma, |
SK-MEL-28 |
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in-vitro, |
Melanoma, |
A375 |
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LDHA↓, both baicalein and baicalin inhibited LDHα expression in Mel586, A375, and B16F0 melanoma cells, and ENO1 expression in SK-MEL-2 and A375 cells, as well as partially suppressed PKM2 expression in SK-MEL-2, A375, and B16F0 tumor cells
ENO1↓,
PKM2↓,
GLUT1↓, Baicalein and baicalin treatments markedly suppressed gene expression of Glut1, Glut3, HK2, TPI, GPI, and PFK1 in both human and mouse melanoma cells
GLUT3↓,
HK2↓,
PFK1↓,
GPI↓,
TPI↓,
GlucoseCon↓, baicalein and baicalin significantly inhibited glucose uptake abilities of four melanoma cell lines no matter of N-RAS and B-RAF mutation statuses
TumCG↓, baicalein and baicalin strongly suppressed tumor growth and proliferation of both human and mouse melanoma cells
TumCP↓,
mTORC1↓, Down-Regulation of mTORC1-HIF1α Signaling in Melanoma Cells Is Responsible for Glucose Metabolism Inhibition Induced by Baicalein and Baicalin
Hif1a↓,
Ki-67↓, We observed that baicalein and baicalin treatments markedly suppressed tumor cell proliferation as indicated by a decrease of Ki-67+ cell populations in tumor tissues
Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,
Hif1a↓, in the human primary cultured glioma cells borneol regulated HIF-1a expression via mTORC1/eIF4E pathway.
Apoptosis↑, The higher the concentration of borneol, the greater the apoptosis rate
mTORC1↓, HIF-1 α, mTORC1, eIF4E and Bcl-2 were treated with four different concentrations (10, 20, 40, 80 μg/ml) of borneol for 24 hours MRNA expression level showed a downward trend
EIF4E↓,
Bcl-2↓,
BAX↑, the expression of Bax and caspase-3 protein showed an upward trend,
Casp3↑,
ChemoSen↑, borneol can cooperate with chemotherapy drugs by activating ROS mediated oxidative damage.
ROS↑,
RadioS↑, We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo.
Beclin-1↑, coincided with increased expression of beclin-1 and LC3.
Hif1a↓, And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E.
mTORC1↓,
EIF4E↓,
TumAuto↑, Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.
AntiCan↑, Borneol is a multifaceted anticancer agent with intrinsic cytotoxic activity;
Apoptosis↑, via diverse mechanisms such as apoptosis induction, mitochondrial dysfunction, ROS generation
mtDam↑,
ROS↑,
mTORC1↓, and inhibition of oncogenic pathways, including mTORC1/eIF4E/HIF-1α, NF-κB, STAT3, and PI3K/Akt.
EIF4E↓,
Hif1a↓,
NF-kB↓,
STAT3↓,
PI3K↓,
Akt↓,
ChemoSen↑, borneol demonstrates significant synergistic effects when combined with established chemotherapeutic agents like temozolomide, doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil,
BioEnh↑, enhancing drug uptake, overcoming resistance, and amplifying apoptosis, especially in drug-resistant and brain tumor models.
BioAv↑, borneol possesses high intestinal absorption, BBB permeability, moderate toxicity, and compliance with Lipinski's Rule of Five.
BBB↑,
toxicity↝,
*CRM↓, AcCoA depleting agents (e.g., hydroxycitrate),
*Dose?, acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine)
*AntiAge↑, Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage.
*Acetyl-CoA↓, Altogether, these observations point to the idea that starvation causes autophagy because it results in the early depletion of AcCoA
*SIRT1↑, nduction of the deacetylase activity of sirtuins (as a result of changing NADH/NAD+ ratios and increased SIRT1 expression)
*AMPK↑, activation of AMPK activity (as a result of changing ATP/ADP ratios)
*mTORC1↓, inhibition of MTORC1 (as a result of amino acid depletion).
*AntiAge↑, CR or intermittent fasting are known for their wide life-span-extending
chemoP↑, fasting can reduce the subjective and objective toxicity of cytotoxic anticancer chemotherapies, both in humans and in mouse models, at the same time that it improves treatment outcome in mice
mTORC1↓, While fasting-mimicking diet (FMD) enhances the activity of anticancer agents by inhibiting the mTORC1 signaling
IGF-1↓, FMD cooperated with CDK4/6i to suppress the levels of IGF1 and RAS.
RAS↓,
OS↑, dietary methionine restriction may have a beneficial effect on lifespan extension and metabolic health.
mTORC1↓, In contrast, methionine may activate mTORC1 and suppress autophagy.
TumAuto↑,
Risk↓, IF has shown potential for reducing cancer risk and enhancing therapeutic efficacy by sensitizing tumor cells to chemotherapy and radiotherapy.
ChemoSen↑, intermittent fasting (IF) may enhance the effectiveness of chemotherapy and targeted therapies by activating autophagy. IF enhances the effectiveness of chemotherapy, including drugs such as cisplatin, cyclophosphamide, and doxorubicin
RadioS↑, disease stabilization, improved response to radiotherapy patients with glioma
*Dose↝, 16:8—16 h of fasting with an 8 h eating window;
*Dose↝, 5:2—consuming a standard number of calories for 5 days and reducing intake to 25% of daily requirements for 2 days;
*Dose↝, Eat–Stop–Eat—complete fasting for 24–48 h.
*LDL↓, IF during Ramadan (approximately 18 h of fasting for 29–30 days) reduces LDL cholesterol levels and increases HDL cholesterol in women, as well as reducing inflammatory markers such as CRP and TNF-α
*CRP↓,
*TNF-α↓,
TumAuto↓, Intermittent fasting activates autophagy as an adaptive mechanism to nutrient deprivation, which may modulate tumor development and treatment
GLUT1↓, fasting reduces the expression of glucose transporters GLUT1/2, which slow down cancer metabolism and increase the susceptibility of cancer cells to oxidative stress
GLUT2↓,
glucose↓, studies on cell and animal models have shown that intermittent fasting reduces glucose and insulin-like growth factor (IGF-1) levels [103], as well as insulin [104,105], resulting in the inhibition of the mTOR kinase pathway (PI3K/Akt/mTOR), suppress
IGF-1↓,
Insulin↓,
mTOR↓,
mTORC1↓, suppression of mTORC1 [22], and activation of AMPK through increased ADP/ATP ratio in cells, which supports autophagy and induces apoptosis
AMPK↑,
Warburg↓, Moreover, IF counteracts the Warburg effect by promoting oxidative phosphorylation, leading to an increase in the production of reactive oxygen species (ROS) and enhanced oxidative stress in cancer cells [106,108], causing DNA damage and the activati
OXPHOS↑,
ROS↑,
DNAdam↑,
JAK1↓, fasting reduces the production of adenosine by cancer cells, inhibiting the activation of the JAK1/STAT pathway, thereby reducing cancer cell proliferation
STAT↓,
TumCP↓,
QoL↑, reduction in IGF-1 levels, improved quality of life patients with multiple cancer types
tumCV↓, Fisetin was significant in suppressing CCA cell viability and colony formation during the course of this experiment.
ChemoSen↑, fisetin significantly potentiated the cisplatin-induced CCA cells death
TumCMig↓, reduced the migration of cancer cells and demonstrated more pronounced effects on KKU-M452
cells
ROS↑, fisetin prompted cell death and apoptosis in CCA cells by stimulating the generation of ROS in KKU-100 cells at a dosage of 50 μM
TumCI↓, suppression of cell invasion and migration,prevention of angiogenesis
angioG↓,
CDK2↓, mechanisms including the suppression of cyclin-dependent kinases, the inhibition of PI3K/Akt/mTOR
PI3K↓,
Akt↓,
mTOR↓,
EGFR↓, suppression of the EGFR pathway, the stimulation of the caspase cascade
Casp↑,
mTORC1↓, suppressing the mTORC1 and 2 signaling
mTORC2↑,
cycD1/CCND1↓, decreasing
the level of the cyclin D1 and cyclin E mRNA
cycE/CCNE↓,
MMP2↓, Matrix metalloproteinases (MMP) 2 and MMP 9 gene expression and enzyme activity are suppressed
MMP9↓,
ER Stress↑, Moreover, fisetin also caused endoplasmic reticulum (ER) stress-induced production of mitochondrial ROS generation and Ca2+, with the involvement of MAPK signaling
Ca+2↑,
eff↓, The ROS scavenger molecule N-acetyl cysteine decreased fisetin-activated apoptosis in multiple
myeloma and oral cancer cells
tumCV↓, Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by signifi-cantly inducing the expression of Caspases- 3,-8 and -9 and pro-apoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2
Apoptosis↑,
Casp3↑,
Casp8↑,
Casp9↑,
BAX↑,
BAD↑,
Bcl-2↓,
Bcl-xL↓,
PI3K↓, inhibited PI3K/Akt pathway and ERK1/2,
Akt↓,
ERK↓,
p‑JNK↑, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38
p‑cJun↑,
p‑p38↑,
ROS↑, Fisetin-induced ROS generation and decrease in mitochondrial membrane potential
MMP↓, noticeable decline of mitochondrial transmembrane potential (ΔΨm) in a dose-dependent manner
mTORC1↓, fisetin at various concentrations (20-100 μM) caused a significant (p<0.05) decrease in the level of p-Akt and mTORC1 (an important effector protein of Akt), while up-regulated PTEN.
PTEN↑,
p‑GSK‐3β↓, Level of phosphorylated glycogensynthase kinase 3ǃ (GSK3ǃ), (a serine/threonine kinase) and
cyclin D1 were potentially decreased by fisetin which is in line with raised non-phosphorylated levels of GSK3ǃ
GSK‐3β↑,
NF-kB↓, Down-regualtion of NF-κB along with significant up-regulations in IκB upon fisetin treatment correlates with the down-regulation of p-Akt levels.
IKKα↑,
Cyt‑c↑, activates the efflux of cytochrome C
*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
*p‑cMyc↑,
*NRF2↑,
*GSH↑,
*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
PI3K↓,
Akt↓,
TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
p27↑,
JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
MMP2↓,
MMP9↓,
uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
cFos↓,
cJun↓,
E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
Vim↓,
N-cadherin↓,
EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
Cyt‑c↑,
Diablo↑,
Casp↑,
cl‑PARP↑,
P53↑, fisetin with induction of p53 protein
COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
PGE2↓,
HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
HSP27↓,
DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
Casp3↑,
Casp9↑,
ROS↑, This was associated with production of intracellular ROS
AMPK↑, Fisetin induced AMPK signaling
NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
Ca+2↑,
mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
p70S6↓,
ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
IRE1↑,
ATF4↑,
GRP78/BiP↑,
eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer
half-life of 3.12 h.
*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h
*neuroP↑, As a hydrophobic agent, FIS readily penetrates cell membranes and accumulates in cells to exert neuroprotective, neurotrophic and antioxidant effects
*antiOx↑,
*Inflam↓, FIS treatment may include alleviating inflammation, cell apoptosis and oxidative stress
RenoP↑, alleviates cell apoptosis and inflammation in acute kidney injury
COX2↓, FIS induces apoptosis in various tumor cells by, for example, inhibiting cyclooxygenase-2, inhibiting the Wnt/EGFR/NF-κB pathway, activating the caspase-3 cascade
Wnt↓,
EGFR↓,
NF-kB↓,
Casp3↑,
Ca+2↑, activating the caspase-3 and Ca2+ dependent endonuclease, and activating the caspase-8/caspase-3 dependent pathway via ERK1/2.
Casp8↑,
TumCCA↑, FIS controls the cell cycle and inhibits cyclin-dependent kinases (CDKs) in human cancer cell lines,
CDK1↓,
PI3K↓, by inhibition of PI3K/Akt/mTOR signaling [20], mitogen-activated protein kinases (MAPK) [21], and nuclear transcription factor (NF-κB)
Akt↓,
mTOR↓,
MAPK↓,
*P53↓, FIS inhibits aging by reducing p53, p21 and p16 expression in mouse and human tissues
*P21↓,
*p16↓,
mTORC1↓, FIS induces autophagic cell death by inhibiting both the mTORC1 and mTORC2 pathways
mTORC2↓,
P53↑, FIS significantly increases the expression of p53 and p21 proteins and lowers the levels of cyclin D1 [27,28], cyclin A, CDK4 and CDK2, thus contributing to cell-cycle arrest.
P21↑,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
BAX↑, FIS also increases Bax [27,28] and Bak [27] protein expression, but reduces the levels of Bcl-2 [27,28], Bcl-xL [27] and PCNA [28], and then starts the mitochondrial apoptotic pathway.
Bcl-2↓,
PCNA↓,
HER2/EBBR2↓, FIS reduces HER2 tyrosine phosphorylation in a dose-dependent manner and aids in proteasomal degradation of HER2 rather than lysosomal degradation
Cyt‑c↑, FIS cells causes destabilization of the mitochondrial membrane and an increase in cytochrome c levels, which is consistent with the loss of mitochondrial membrane integrity.
MMP↓,
cl‑Casp9↑,
MMP2↓, FIS reduces the enzymatic activity of both MMP-2 and MMP-9.
MMP9↓,
cl‑PARP↑, cell membrane, mitochondrial depolarization, activation of caspase-7, -8 and -9, and cleavage of PARP
uPA↓, interestingly, the promoter activity of the uPA gene is suppressed by FIS
DR4↑, induces upregulation of DR4 and DR5 death receptor expression in a dose-dependent manner
DR5↑,
ROS↓, FIS induces an increase in intracellular Ca2+ but reduces the production of ROS in WEHI-3 cells (myelomonocytic leukemia)
AIF↑, It also increases the levels of caspase-3 and AIF mRNA, but also increases necrosis markers including RIP3 and PARP1
CDC25↓, FIS reduces the expression of cdc25a, but increases the expression of p-p53, Chk1, p21 and p27, which may lead to a G0/G1 arrest.
Dose↑, FIS in concentrations from 0 to 10 μM does not affect cell viability; however, its use at concentrations of 20–40 μM significantly reduces the viability of lung cancer cells
CHOP↑, CaKi : FIS induces upregulation of CHOP expression and ROS production
ROS↑, NCI-H460 :FIS increases the ER stress signaling FIS increases the level of mitochondrial ROS FIS induces mitochondrial Ca2+ overloading and ER stress FIS induced ER stress-mediated cell death via activation of the MAPK pathway
cMyc↓, FIS influences proliferation related genes such as cyclin D1, c-myc and cyclooxygenase (COX)-2 by downregulating them.
cardioP↑, cardioprotective activity
DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
ROS↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
cl‑Casp3↑,
Cyt‑c↑, leading to cytochrome-c release
lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
TumCMig↓,
TumCI↓,
uPA↓,
ERK↓,
MMP9↓,
NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
cFos↓,
cJun↓,
AP-1↓,
TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
mTORC2↓,
TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
TGF-β↓,
EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
Akt↓,
mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
IRE1↑,
ATF4↑,
GRP78/BiP↑,
ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
cycE/CCNE↓,
cycD1/CCND1↓,
P21↑,
COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
Wnt↓,
EGFR↓,
β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
TCF-4↓,
MMP7↓,
RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2
Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.
TumCP↓, Niclosamide was found to inhibit adrenocortical carcinoma cellular proliferation, which was associated with apoptosis, reduction of epithelial-to-mesenchymal transition and β-catenin levels.
Apoptosis↑,
EMT↓,
β-catenin/ZEB1↓,
TumCG↓, Oral administration of niclosamide led to tumor growth inhibition with no observed toxicity.
toxicity↓,
Wnt↓, Lu et al. reported that niclosamide inhibits Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in breast cancer cells [11].
LRP6↓,
eff↑, niclosamide acts synergistically with a monoclonal antibody that specifically activates TRAIL death receptor 5 to inhibit tumor growth of basal-like breast cancers [12].
DR5↑,
mTORC1↓,
pH↓, Niclosamide lowered the cytoplasmic pH and may indirectly lead to inhibition of mTORC1 signaling [13]
CSCs↓, Niclosamide also was found to prevent the conversion of non-breast cancer stem cells into cancer stem cells
IL6↓, This mechanism is associated with inhibition of the IL6-JAK1-STAT3 signal transduction pathway
JAK1↓,
STAT3↓, Ren et al. identified niclosamide as a potent STAT3 inhibitor able to suppress STAT3 transcriptional activity
ChemoSen↑, niclosamide alone or in combination with cisplatin represses the growth of xenografts of cisplatin-resistant triple-negative breast cancer cells.
TumCG↓, Niclosamide inhibited growth of colon cancer cells from human patients both in vitro and in vivo, regardless of mutations in APC [24].
tumCV↓, niclosamide selectively inhibited glioblastoma cell viability [29]. Detailed mechanism studies revealed that niclosamide suppressed the Wnt, Notch, mTOR, and NF-κB signaling pathways.
NOTCH↓,
NF-kB↓,
EGFR↓, Li et al. reported that inhibition of EGFR by erlotinib, an FDA-approved therapeutic agent, led to activation of STAT3 signaling in head and neck cancer cells
ROS↑, niclosamide inhibits TNF-α-induced NF-κB–dependent reporter activity and increased the levels of reactive oxygen species (ROS) in AML cells.
RadioS↑, niclosamide enhanced radiosensitivity of the non-small cell lung cancer cell line H1299.
cFos↓, inhibit osteosarcoma cell proliferation, migration, and survival. This inhibitory effect is associated with decreased expression of c-Fos, c-Jun. E2F1, and c-Myc.
cJun↓,
E2Fs↓,
cMyc↓,
Half-Life↓, Niclosamide exhibits a short half-life (6.0 ± 0.8 h). Niclosamide was rapidly absorbed with a Tmax of less than 30 min. The Cmax is 354 ± 152 ng/mL.
BioAv↝, AUC and bioavailability were 429 ± 100 and 10%, respectively. In order to make more effective use of niclosamide, additional work needs to be done to improve its solubility, absorption and systemic bioavailability.
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in-vitro, |
BC, |
MCF-7 |
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in-vitro, |
Pca, |
PC3 |
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in-vitro, |
Pca, |
DU145 |
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in-vitro, |
BC, |
MDA-MB-231 |
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in-vitro, |
Nor, |
HEK293 |
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Wnt↓, salinomycin was not only a potent Wnt/β-catenin signaling inhibitor, bus also a strong mTORC1 signaling antagonist in breast and prostate cancer cells.
β-catenin/ZEB1↓,
mTORC1↓, SALINOMYCIN INHIBITS MTORC1 SIGNALING IN BREAST AND PROSTATE CANCER CELLS
GSK‐3β↑, Mechanistically, salinomycin activated GSK3β in cancer cells.
cycD1/CCND1↓, salinomycin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/β-catenin and mTORC1 signaling, in prostate and breast cancer cells,
survivin↓,
LRP6↓, SALINOMYCIN INHIBITS LRP6 EXPRESSION AND WNT/β-CATENIN SIGNALING IN BREAST CAND PROSTATE CANCER CELLS
TumCG↓, SALINOMYCIN INHIBITS BREAST AND PROSTATE CANCER CELL GROWTH AND INDUCES CANCER CELL APOPTOSIS
Apoptosis↑,
*EP300↓, potent autophagy inducers including spermidine de facto act as EP300 inhibitors.
*mTORC1↓, simultaneously inhibit mTORC1.
*CRM↑, caloric restriction or intermediate fasting,7 continuous or intermittent medication of rapamycin,8, 9, 10 administration of the sirtuin 1-activator resveratrol,11, 12 external supply of the polyamine spermidine,
*HATs↓, Spermidine turned out to be an efficient inhibitor of histone acetyltransferases in vitro
*p62↓, Moreover, all the mentioned acetyltransferase inhibitors induced a significant reduction of p62/SQSTM1 levels,
*AntiAge↑, Spermidine retards the manifestation of several major age-associated diseases including arterial aging,36 colon cancer37 and neurodegenerative processes in mice
AntiCan↑,
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in-vitro, |
Bladder, |
T24/HTB-9 |
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in-vitro, |
Bladder, |
J82 |
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Glycolysis↑, Vitamin K2 renders bladder cancer cells more dependence on glycolysis than TCA cycle
GlucoseCon↑, results suggest that Vitamin K2 is able to induce metabolic stress, including glucose starvation and energy shortage, in bladder cancer cells, upon glucose limitation.
lactateProd↑,
TCA↓, Vitamin K2 promotes glycolysis and inhibits TCA cycle in bladder cancer cells
PI3K↑,
Akt↑,
AMPK↑, Vitamin K2 remarkably activated AMPK pathway
mTORC1↓,
TumAuto↑,
GLUT1↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
HK2↑,
LDHA↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
ACC↓, Vitamin K2 remarkably decreased the amounts of Acetyl coenzyme A (Acetyl-CoA) in T24 cells
PDH↓, suggesting that Vitamin K2 inactivates PDH
eff↓, Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death.
cMyc↓, c-MYC protein level was also significantly reduced in T24 cells following treatment with Vitamin K2 for 18 hours
Hif1a↑, Besides, the increased expression of GLUT-1, HIF-1α, p-AKT and p-AMPK were also detected in Vitamin K2-treated tumor group
p‑Akt↑,
eff↓, 2-DG, 3BP and DCA-induced glycolysis attenuation significantly prevented metabolic stress and rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
eff↓, inhibition of PI3K/AKT and HIF-1α notably attenuated Vitamin K2-upregulated glycolysis, indicating that Vitamin K2 promotes glycolysis in bladder cancer cells via PI3K/AKT and HIF-1α signal pathways.
eff↓, (NAC, a ROS scavenger) not only alleviated Vitamin K2-induced AKT activation and glycolysis promotion, but also significantly suppressed the subsequent AMPK-dependent autophagic cell death.
eff↓, glucose supplementation not only restored c-MYC expression, but also rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
ROS↑, under glucose limited condition, the increased glycolysis inevitably resulted in metabolic stress, which augments ROS accumulation due to lack of glucose for sustained glycolysis.
Showing Research Papers: 1 to 21 of 21
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
lipid-P↓, 1, NRF2↑, 2, OXPHOS↑, 1, ROS↓, 3, ROS↑, 12, mt-ROS↑, 1, SIRT3↑, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 1, CDC2↓, 1, CDC25↓, 2, EGF↓, 1, Insulin↓, 1, MEK↓, 1, MMP↓, 6, mtDam↑, 1, Raf↓, 1, c-Raf↓, 1,
Core Metabolism/Glycolysis ⓘ
ACC↓, 1, AMPK↑, 6, ATG7↑, 1, cMyc↓, 4, ENO1↓, 1, glucose↓, 1, GlucoseCon↓, 1, GlucoseCon↑, 1, GLUT2↓, 1, Glycolysis↓, 1, Glycolysis↑, 1, GPI↓, 1, HK2↓, 1, HK2↑, 1, lactateProd↑, 1, LDHA↓, 1, LDHA↑, 1, PCK1↓, 1, PDH↓, 1, PFK1↓, 1, PKM2↓, 1, p‑S6K↓, 1, TCA↓, 1, TPI↓, 1, Warburg↓, 1,
Cell Death ⓘ
Akt↓, 7, Akt↑, 1, p‑Akt↑, 1, Apoptosis↑, 6, BAD↑, 1, BAX↑, 5, Bax:Bcl2↑, 1, Bcl-2↓, 6, Bcl-xL↓, 1, Casp↑, 3, Casp3↑, 6, cl‑Casp3↑, 1, Casp8↑, 2, Casp9↑, 4, cl‑Casp9↑, 2, Chk2↑, 1, Cyt‑c↑, 5, Diablo↑, 2, DR4↑, 1, DR5↑, 4, Fas↑, 1, IAP2↓, 1, JNK↑, 2, p‑JNK↑, 1, MAPK↓, 3, Mcl-1↑, 1, p27↑, 2, p‑p38↓, 1, p‑p38↑, 1, survivin↓, 3, Telomerase↓, 1,
Kinase & Signal Transduction ⓘ
EF-1α↓, 1, HER2/EBBR2↓, 1, p70S6↓, 1, TSC2↑, 1,
Transcription & Epigenetics ⓘ
cJun↓, 3, cJun↑, 1, p‑cJun↑, 1, H3↑, 1, p‑H3↓, 1, H4↑, 1, HATs↑, 1, tumCV↓, 3,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, cl‑CHOP↑, 1, ER Stress↑, 4, GRP78/BiP↑, 3, HSP27↓, 1, HSP70/HSPA5↓, 1, IRE1↑, 2,
Autophagy & Lysosomes ⓘ
ATG5↑, 2, Beclin-1↑, 2, LC3II↑, 1, LC3s↑, 1, TumAuto↓, 1, TumAuto↑, 3,
DNA Damage & Repair ⓘ
ATM↑, 1, CHK1↑, 1, DNAdam↑, 4, P53↑, 3, cl‑PARP↑, 4, PCNA↓, 3,
Cell Cycle & Senescence ⓘ
CDK1↓, 1, CDK2↓, 7, CDK4↓, 6, cycA1/CCNA1↓, 1, cycD1/CCND1↓, 8, cycE/CCNE↓, 4, E2Fs↓, 1, P21?, 1, P21↑, 3, p‑RB1↓, 1, TumCCA↑, 6,
Proliferation, Differentiation & Cell State ⓘ
CD133↓, 2, cFos↓, 3, CSCs↓, 3, Diff↓, 1, EIF4E↓, 3, EMT↓, 5, ERK↓, 3, GSK‐3β↑, 3, p‑GSK‐3β↓, 1, HDAC↓, 1, IGF-1↓, 2, LRP6↓, 2, mTOR↓, 5, mTORC1↓, 18, p‑mTORC1↓, 1, mTORC2↓, 3, mTORC2↑, 1, n-MYC↓, 1, Nanog↓, 1, Nestin↓, 2, NOTCH↓, 2, NOTCH1↓, 1, NOTCH3↓, 1, OCT4↓, 1, PI3K↓, 8, PI3K↑, 1, PTEN↑, 2, RAS↓, 2, SOX2↓, 2, STAT↓, 1, STAT3↓, 5, TCF-4↓, 1, TumCG↓, 6, Wnt↓, 4,
Migration ⓘ
AP-1↓, 1, Ca+2↑, 4, E-cadherin↑, 2, Ki-67↓, 2, MMP13↓, 1, MMP2↓, 4, MMP7↓, 2, MMP9↓, 5, MMPs↓, 2, N-cadherin↓, 1, Rho↓, 1, SOX4↓, 1, TGF-β↓, 1, TumCA↓, 1, TumCI↓, 3, TumCMig↓, 3, TumCP↓, 3, TumMeta↓, 1, uPA↓, 5, Vim↓, 1, Zeb1↓, 1, β-catenin/ZEB1↓, 3, β-catenin/ZEB1↑, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 2, ATF4↑, 2, EGFR↓, 5, Hif1a↓, 6, Hif1a↑, 1, NO↑, 1, VEGF↓, 2, VEGFR2↓, 3,
Barriers & Transport ⓘ
BBB↑, 1, GLUT1↓, 2, GLUT1↑, 1, GLUT3↓, 1, P-gp↓, 2,
Immune & Inflammatory Signaling ⓘ
CCR7↓, 1, COX2↓, 5, CXCR4↓, 1, IKKα↓, 1, IKKα↑, 1, IL6↓, 2, Inflam↓, 1, JAK1↓, 3, JAK2↓, 1, MCP1↓, 1, NF-kB↓, 8, p65↓, 1, PGE2↓, 4, TNF-α↓, 1,
Cellular Microenvironment ⓘ
pH↓, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1, CDK6↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, BioAv↑, 1, BioAv↝, 1, BioEnh↑, 1, ChemoSen↑, 9, Dose?, 1, Dose↓, 1, Dose↑, 2, Dose↝, 2, eff↓, 6, eff↑, 10, eff↝, 1, Half-Life↓, 3, Half-Life↝, 2, RadioS↑, 6, selectivity↑, 2,
Clinical Biomarkers ⓘ
AR↓, 1, EGFR↓, 5, HER2/EBBR2↓, 1, IL6↓, 2, Ki-67↓, 2,
Functional Outcomes ⓘ
AntiCan↑, 2, cardioP↑, 1, chemoP↑, 2, hepatoP↑, 1, neuroP↑, 1, OS↑, 2, QoL↑, 1, RenoP↑, 2, Risk↓, 1, toxicity↓, 1, toxicity↝, 1,
Total Targets: 235
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 3, GSH↑, 1, HO-1↑, 1, NRF2↑, 1, ROS↓, 1,
Core Metabolism/Glycolysis ⓘ
Acetyl-CoA↓, 1, AMPK↑, 1, p‑cMyc↑, 1, CRM↓, 1, CRM↑, 1, LDL↓, 1, SIRT1↑, 1,
Transcription & Epigenetics ⓘ
HATs↓, 1,
Autophagy & Lysosomes ⓘ
p62↓, 1,
DNA Damage & Repair ⓘ
p16↓, 1, P53↓, 1,
Cell Cycle & Senescence ⓘ
P21↓, 1,
Proliferation, Differentiation & Cell State ⓘ
EP300↓, 1, ERK↑, 1, mTORC1↓, 2,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
CRP↓, 1, Inflam↓, 4, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
Dose?, 1, Dose↝, 3,
Clinical Biomarkers ⓘ
CRP↓, 1,
Functional Outcomes ⓘ
AntiAge↑, 3, neuroP↑, 2,
Total Targets: 30
Scientific Paper Hit Count for: mTORC1, mammalian target of rapamycin complex 1
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#:440 State#:% Dir#:1
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