- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Angelica Polysaccharide Resists Platelets Apoptosis Induced by LY294002 (Pubmed Central) - Aug 29, 2019
APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.
- |||||||||| Somavert (pegvisomant) / Pfizer, quercetin (LY294002) / Eli Lilly
Preclinical, Journal: IGF1 suppresses cholesterol accumulation in the liver of growth hormone deficient mice via the activation of ABCA1. (Pubmed Central) - Aug 28, 2019
...The activity of a reporter construct containing the ABCA1 promoter was induced by IGF1, and this effect was blocked by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K)...For in vivo experiments, we used an inhibitor for the GH receptor (Pegvisomant) to reduce the IGF1 level...IGF1-treatment stimulated ABCA1 expression to improve cholesterol accumulation in these mice. These results show that the PI3K/Akt/FoxO1 pathway contributes to the regulation of ABCA1 expression in response to IGF1-stimulation that suppressed FL in GH-deficient mice.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: FABP5 regulates the proliferation of clear cell renal cell carcinoma cells via the PI3K/AKT signaling pathway. (Pubmed Central) - Aug 28, 2019
...In addition, treatment with the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K)/AKT inhibitor, LY294002, attenuated the pro‑proliferative effects of exogenous FABP5 expression in Caki‑1 and 786O cells...Furthermore, FABP5 was observed to regulate tumor growth in nude mice in vivo. In conclusion, the results of the present study suggest that FABP5 may exert a pro‑proliferative role in ccRCC and may be associated with malignant progression and tumorigenesis.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Protective effect of Schisandra chinensis lignans on hypoxia-induced PC12 cells and signal transduction. (Pubmed Central) - Aug 25, 2019
...The expression of p-Akt protein in the presence of PI3K/Akt signaling pathway inhibitor LY294002 and SCL was not markedly changed indicating that signal transduction was affected by this Chinese herb...Data suggest that the protective effect exerted by SCL in hypoxia-induced PC12 cell injury involves enhanced cell proliferation and inhibition of apoptosis mediated by activation of PI3K/Akt signaling pathway. The increased protein Akt phosphorylation expression levels resulted in consequent reduced downstream caspase-3 expression and enhanced Bcl-2 expression.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Protosappanin-A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT-mTOR signaling. (Pubmed Central) - Aug 24, 2019
...Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K-AKT inhibitor)...PrA and OA were also seen to inhibit podocyte apoptosis and p-AKT/p-mTOR levels induced by IGF-1 (a PI3K-AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT-mTOR signaling.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Effects of scalp electroacupuncture on the PI3K/Akt signalling pathway and apoptosis of hippocampal neurons in a rat model of cerebral palsy. (Pubmed Central) - Aug 23, 2019
Basso, Beattie and Bresnahan (BBB) locomotor scores, hippocampal protein expression of Akt and p-Akt (by Western blot analysis) and neuronal apoptosis in hippocampal tissue (by histopathology) were assessed at 7, 14 and 21 days post-CP induction.Results CP rats receiving scalp EA treatment demonstrated improved behavioural scores, less hippocampal neuronal apoptosis and higher expression levels of Akt and p-Akt (p<0.05) at all time points studied compared with untreated CP rats. There were no significant differences observed between CP+EA+LY294002 and untreated CP model groups.Conclusions The effects of scalp EA on the PI3K/ Akt signalling pathway may represent one of the mechanisms involved in the inhibition of hippocampal neuronal apoptosis and improvement of deficits associated with CP in a rat model.
- |||||||||| veliparib (ABT-888) / AbbVie, quercetin (LY294002) / Eli Lilly
Pivotal Role of Chitinase-3-like Protein 1, a Novel Myokine in Exercise Training-Induced Protection Against Cardiomyocyte Apoptosis and Promotion of Angiogenesis After Myocardial Infarction in Rats (Zone 4, Science and Technology Hall) - Aug 21, 2019 - Abstract #AHA2019AHA_6399;
H9C2 and HUVEC cells were treated in vitro with AMPK agonist (AICAR, as exercise memetic, 2 mM 24 h), recombinant human CHI3L1 (rhCHI3L1, 150 ng/ml 24 h), and lipopolysaccharide (LPS, as inflammation inducer, 10 μg/ml 4 h), PAR2 receptor blocker (Veliparib, 10 μM 1 h), or PI3K inhibitor (LY294002, 10 μg/ml 40 min), respectively. post-MI exercise training activated CHI3L1/PAR2 signaling pathway and induced PI3K-Akt, ERK, Bcl2, eNOS, which inhibited cardiac apoptosis and promoted LV function and angiogenesis in post-MI hearts.
- |||||||||| quercetin (LY294002) / Eli Lilly
Heart Enriched IRF2BP2 Protects Cardiomyocytes Against Hypoxia in vitro (Zone 1, Science and Technology Hall) - Aug 21, 2019 - Abstract #AHA2019AHA_5476;
PI3-kinase was inhibited by its inhibitor, LY294002(30μM)... The PI3-kinase/Akt activated, heart-enriched IRF2BP2 could protect cardiac cells against hypoxia via its target gene KLF-2.
- |||||||||| MK-2206 / Merck (MSD), quercetin (LY294002) / Eli Lilly, Acomplia (rimonabant) / Sanofi
Journal: Anandamide Induces Platelet Nitric Oxide Synthase through AMP-Activated Protein Kinase. (Pubmed Central) - Aug 17, 2019
SR144528, an antagonist of type 2 cannabinoid receptor (CB2), has a less-potent effect, suggesting that the CB1 receptor is overall involved in the AEA effect. In conclusion, we show that the CaMKKβ/AMPKα pathway, downstream of the PI3K/AKT pathway, is activated by AEA in human platelets and leads to increase NO levels producing beneficial effects during ischemic conditions and contributing to extend platelet survival.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Klotho protein inhibits H2O2-induced oxidative injury in endothelial Cells via regulation of PI3K/Akt/Nrf2/HO-1 Pathways. (Pubmed Central) - Aug 17, 2019
Klotho protein also activated phosphorylation of AKT, whereas the addition of LY294002, a pharmacological inhibitor of PI3K, blocked KL (klotho protein)-induced Nrf2/HO-1 activation and cytoprotection. Klotho protein enhanced the antioxidant defense ability of the cells by activating the PI3K/AKT pathway, which upregulated the expression of NRF2/HO-1, thereby inhibiting H2O2-induced oxidative damage.
- |||||||||| vincristine / generics
Journal: Wnt5a modulates vincristine resistance through PI3K/Akt/GSK3β signaling pathway in human ovarian carcinoma SKOV3/VCR cells (Pubmed Central) - Aug 16, 2019
Meanwhile, LY294002 (PI3K inhibitor) decreased the protein expression levels of MDR1, β-catenin and Survivin, as well as the phosphorylation levels of Akt and GSK3β in SKOV3/VCR cells (P < 0.05). These results suggest that WNT5A gene silencing reverses VCR resistance in SKOV3/VCR cells possibly through blocking the PI3K/Akt/GSK3β/β-catenin signaling pathway, and thus down-regulating the protein expression levels of MDR1 and Survivin.
- |||||||||| MK-2206 / Merck (MSD), quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Neuroprotective Effect and Mechanism of Action of Tetramethylpyrazine Nitrone for Ischemic Stroke Therapy. (Pubmed Central) - Aug 15, 2019
In addition, LY-294002 (a PI3K inhibitor) and MK2206 (an Akt inhibitor) significantly blocked the protective effect of TBN against OGD-induced death of cortical neurons. Taken together, the multifunctional mechanisms including scavenging free radicals, blocking calcium overload, maintaining mitochondrial function and activating the PI3K/Akt/p-GSK3β cell survival pathway were possibly involved in the neuroprotective effects of TBN, making it a promising clinical candidate for the treatment of ischemic stroke.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: LGI3 promotes human keratinocyte differentiation via the Akt pathway. (Pubmed Central) - Aug 15, 2019
A specific inhibitor of phosphoinositide 3-kinase, LY294002, reduced LGI3-induced expression of differentiation markers in HaCaT cells. Taken together, these results suggest that LGI3 promotes keratinocyte differentiation and could be used as a therapeutic agent to recover skin barrier function in epidermal barrier disruption.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: FoxO1 enhances differentiation and apoptosis in human primary keratinocytes. (Pubmed Central) - Aug 15, 2019
...IGF-1 downregulated FoxO1 and involucrin but upregulated p-Akt expression in HPKs, which was blocked by pretreatment with LY294002...IGF-1 may reduce keratinocyte differentiation through PI3K/Akt/FoxO1 pathway, while isotretinoin can reinforce FoxO1 expression. FoxO1 may be involved in acne pathogenesis and could serve as a potential therapeutic target.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade. (Pubmed Central) - Aug 15, 2019
...In addition, LY294002, a PI3-K inhibitor, was used to investigate the role of AKT/β-catenin signaling in the antidepressant effects of KFL...These results confirmed that KFL exerted antidepressive effects, which might be mediated, at least in part, by enhanced antioxidant abilities and anti-inflammation effects via up-regulation AKT/β-catenin cascade activity in the prefrontal cortex of CSDS mice. Thus, KFL might be a promising, effective, and safe food medicine for depression treatment.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival. (Pubmed Central) - Aug 15, 2019
...While PI3K inhibitor (LY294002) was without effect on cell survival or P38 MAPK activation, it inhibited ghrelin induced ERK1/2 phosphorylation...Of note, podocytes contribute to the formation and the maintenance of the glomerular filtration barrier and thus are important for normal renal function. Therefore, ghrelin secretion in the context of obesity could be involved in the aetiology of kidney injury, a well-known hallmark found in obese patients.
- |||||||||| sirolimus / generics
Journal: Curcumin-Induced Autophagy Augments Its Antitumor Effect against A172 Human Glioblastoma Cells. (Pubmed Central) - Aug 14, 2019
Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Exosomal microRNA-21-5p Mediates Mesenchymal Stem Cell Paracrine Effects on Human Cardiac Tissue Contractility. (Pubmed Central) - Aug 11, 2019
Mechanistically, cotreating with miR-21-5p and LY294002, a PI3K inhibitor, suppressed these effects...Finally, mathematical simulations predicted the translational capacity for miR-21-5p treatment to restore calcium handling in mature ischemic adult human cardiomyocytes.miR-21-5p plays a key role in hMSC-exo-mediated effects on cardiac contractility and calcium handling, likely via PI3K signaling. These findings may open new avenues of research to harness the role of miR-21-5p in optimizing future stem cell-based cardiotherapies.
- |||||||||| loratadine / Sedico, Remedica, generics, Merck (MSD), Bayer
Journal: Loratadine, an H Antihistamine, Inhibits Melanogenesis in Human Melanocytes. (Pubmed Central) - Aug 10, 2019
Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-βII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Increased ZNF84 expression in cervical cancer. (Pubmed Central) - Aug 9, 2019
ZNF84 expression was increased in CC tissues and associated with tumor size. ZNF84 promoted cell proliferation which might involve Akt signal.
- |||||||||| quercetin (LY294002) / Eli Lilly
Biomarker, Journal: Inhibition of Ca -activated chloride channel ANO1 suppresses ovarian cancer through inactivating PI3K/Akt signaling. (Pubmed Central) - Aug 9, 2019
Mechanistically, ANO1 knockdown attenuated phosphorylation of PI3K/Akt, and inhibition of PI3K/Akt signaling by specific inhibitor LY294002 resulted in suppression of ovarian cancer cells growth promoted by ANO1 expression...Taken together, our findings demonstrate that ANO1 overexpression is involved in the pathogenesis of human epithelial ovarian cancer. Inhibition of ANO1 upregulation or inactivating PI3K/Akt signaling may have therapeutic potential for epithelial ovarian cancer, and the detection of ANO1 expression level in PBMCs from patients may also serve as a biomarker for diagnosis and prognosis of epithelial ovarian cancers.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Pulsed electromagnetic fields stimulating osteogenic differentiation and maturation involves primary cilia-PI3K/AKT pathway (Pubmed Central) - Aug 9, 2019
Inhibition of ANO1 upregulation or inactivating PI3K/Akt signaling may have therapeutic potential for epithelial ovarian cancer, and the detection of ANO1 expression level in PBMCs from patients may also serve as a biomarker for diagnosis and prognosis of epithelial ovarian cancers. PEMF activated the PI3K/AKT signaling pathway through primary cilia on the surface of osteoblasts, then promoted bone formation activity and differentiation.
- |||||||||| cyclophosphamide intravenous / generics
Journal: The Signal Transducer and Activator of Transcription 5B (STAT5B) Gene Promotes Proliferation and Drug Resistance of Human Mantle Cell Lymphoma Cells by Activating the Akt Signaling Pathway. (Pubmed Central) - Aug 3, 2019
...MATERIAL AND METHODS GRANTA-519 human mantle cell lymphoma cells were cultured with and without 10 μM fludarabine dephosphorylated 9-ß-D-arabinofuranosyl-2-fluoroadenine, (2-F-araA) or 10 μM 4-hydroperoxycyclophosphamide (4-HC)...Flow cytometry was used to investigate the cell cycle in MCL cells treated with the specific inhibitor of the Akt pathway, LY294002, and assessed cell cycle and cell apoptosis...Increased expression of STAT5B was associated with increased MCL cell proliferation and reduced cell apoptosis and was associated with drug resistance and activation of Akt. CONCLUSIONS STAT5B promoted cell proliferation and drug resistance in human MCL cells by activating the Akt signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3/NF-κB axis. (Pubmed Central) - Aug 3, 2019
...The expressions of p-PI3K, p-AKT2, and PKM2 were increased when stimulated by epidermal growth factor (EGF); however, these expressions were blocked when inhibited the PI3K by LY294002...Taken together, AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice through PKM2-mediated elevation of STAT3 expression and NF-κB activation. In conclusion, we highlight a novel mechanism of the AKT2-PKM2-STAT3/NF-κB axis in the regulation of ovarian cancer progression, and our work suggested that both AKT2 and PKM2 may be potential targets for the treatment of ovarian cancer.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Ginkgolide B ameliorates myocardial ischemia reperfusion injury in rats via inhibiting endoplasmic reticulum stress. (Pubmed Central) - Aug 3, 2019
Finally, the decreased p-AKT and p-mTOR expressions caused by I/R injury were upregulated by GB and inhibition of PI3K/AKT/mTOR pathway by LY294002 abolished the protective effects of GB on I/R injury, indicating that GB activated PI3K/AKT/mTOR pathway during I/R injury. GB protected against myocardial I/R injury through inhibiting ER stress-induced apoptosis via PI3K/AKT/mTOR signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: TGF‑β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. (Pubmed Central) - Aug 3, 2019
...Alterations in the expression of osteogenesis‑ and migration‑associated genes were evaluated following pre‑treatment with a PI3K/AKT inhibitor (LY294002) and an mTOR/S6K1 inhibitor (rapamycin), with or without TGF‑β1...The present study demonstrated that TGF‑β1 promoted the proliferation, differentiation and migration of human hFOB1.19 osteoblasts, and revealed that TGF‑β1 affected the biological activity of osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. Our findings may provide novel insight to aid the development of bone tissue engineering methods for the treatment of bone injury.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: HSP70 silencing aggravates apoptosis induced by hypoxia/reoxygenation in vitro. (Pubmed Central) - Aug 2, 2019
Pretreating A549 cells with the AKT pathway inhibitor, LY294002 and the ERK pathway inhibitor, U0216 led to a decrease in HSP70 expression. These results indicate that silencing HSP70 may aggravate apoptosis in hypoxia-reoxygenation cell models, potentially via the mitogen-activated protein kinase/ERK and phosphoinositide 3-kinase/AKT signaling pathways.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Journal: Activation of the IGF1 receptor stimulates glycogen synthesis by mink uterine epithelial cells. (Pubmed Central) - Aug 1, 2019
These findings suggest to us that the affects of Eon glycogen synthesis by GMMe cells is mediated through Esr1 and increased responsiveness of the cells to insulin. Because picropodophylotoxin blocked the effects of insulin on glycogen production, and both insulin and IGF1 act through PI3K, it is possible that IGF1 plays a role in glycogen production by these cells.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Alpha-enolase promotes gastric cancer cell proliferation and metastasis via regulating AKT signaling pathway. (Pubmed Central) - Aug 1, 2019
ENO1 could modulate AKT signaling pathway in GC cells and the enhanced proliferation and migration ability induced by ENO1 overexpression was impaired after incubation with PI3K inhibitor Ly294002 in SGC7901 cells. Our data demonstrated that ENO1 enhances GC cell proliferation and metastasis through the protein kinase B (AKT) signaling pathway, indicating that ENO1/AKT signaling axis may serve as a potential target for treatment of GC.
|
