- |||||||||| quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal: Antioxidant mechanism of gastrodin combined with isorhynchophylline in inhibiting MPP~+-induced apoptosis of PC12 cells (Pubmed Central) - Mar 2, 2021
PD98059, LY294002 or LiCl could partially reverse these changes pretreated with gastrodin combined with isorhynchophylline, suggesting that gastrodin combined with isorhynchophylline inhibited MPP~+-induced apoptosis of PC12 cells and oxidative stress through ERK1/2 and PI3 K/GSK-3β signal pathways. Our experiments showed that gastrodin combined with isorhynchophylline could down-re-gulate the mRNA expression of caspase-3 and up-regulate the protein expressions of HO-1 and NQO-1, so as to reduce oxidative stress and inhibit apoptosis.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Short ELF-EMF Exposure Targets SIRT1/Nrf2/HO-1 Signaling in THP-1 Cells. (Pubmed Central) - Feb 27, 2021
Pretreatment with LY294002 (Akt inhibitor) and PD980559 (ERK inhibitor) inhibited LPS-induced Nrf2 nuclear translocation and HO-1 protein expression in ELF-EMF-exposed cells. Taken together, our results suggest that short ELF-EMF exposure exerts a protective role in THP-1 cells treated with an inflammatory/oxidative insult such as LPS, via the regulation of Nrf-2/HO-1 and SIRT1 /NF-kB pathways associated with intracellular glutathione (GSH) accumulation.
- |||||||||| sirolimus / Generic mfg.
Journal: Tetramethylpyrazine ameliorates hepatic fibrosis through autophagy-mediated inflammation. (Pubmed Central) - Feb 25, 2021
Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future. TMP exerts therapeutic effects in hepatic fibrosis mainly through promoting autophagy to ameliorate inflammation by inhibiting the AKT-mTOR signalling pathway, providing a new perspective for the treatment of chronic liver diseases.
- |||||||||| quercetin (LY294002) / Eli Lilly
[VIRTUAL] NOX-4 AND SELENIUM INFLUENCES IN THYROID PI3K SIGNALING IN THYROID CELLS. () - Feb 24, 2021 - Abstract #ICE2021ICE_540;
2-IHDA induced akt phosphorylation (1.8 fold, p<0.05), the PI3K inhibitor (LY294002) and Selenium reverted the inhibitory effect of 2-IHDA on NIS and GPx mRNA gene transcription... These results suggest that NOX4 and Selenium plays a critical role in Akt phosphorylation in FRTL-5 cells that influence NIS expression.
- |||||||||| quercetin (LY294002) / Eli Lilly, Bay11-7082 / InvivoGen
Journal: Low molecular weight-PAHs induced inflammation in A549 cells by activating PI3K/AKT and NF-κB signaling pathways. (Pubmed Central) - Feb 23, 2021
In addition, pro-inflammatory cytokine expressions of TNF-α and IL-6 induced by the binary mixture of Phe and Flu were all alleviated by co-treatment with PI3K/AKT and NF-κB specific inhibitors (LY294002 and BAY11-7082). The results suggested that PI3K/AKT and NF-κB signaling pathways played an important role in LMW-PAHs induced inflammation in A549 cells.
- |||||||||| sirolimus / Generic mfg.
Journal: PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells. (Pubmed Central) - Feb 23, 2021
In addition, p-CREB interacts with p-Smad1/5/9 in MSCs, and p-CREB or p-Smad1/5/9 are both enriched at the promoter region of Wnt10b. Our findings indicate that inhibitory effects of PTEN on BMP9's osteogenic potential may be partially mediated through decreasing the expression of Wnt10b via the disturbance of interaction between CREB and BMP/Smad signaling.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Sulfur dioxide induces vascular relaxation through PI3K/Akt/eNOS and NO/cGMP signaling pathways in rats. (Pubmed Central) - Feb 20, 2021
The results showed that when the dose of SO was 30 μM, the vasodilation of endothelium-intact rings was partially suppressed by LY294002 and N-nitro-l-arginine methyl ester, and the protein levels of phosphoinositide 3-kinase (PI3K), p-Akt, and p-endothelial nitric oxide synthase (p-eNOS) were significantly increased...The results suggest that high concentrations of SO may cause damage to blood vessels. This study will help to further inform the etiologies of SO-related cardiovascular disease.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO biomarker: Isoforsythiaside Attenuates Alzheimer's Disease via Regulating Mitochondrial Function Through the PI3K/AKT Pathway. (Pubmed Central) - Feb 20, 2021
The improved cell viability and mitochondrial function after IFY incubation was blocked by the synthetic PI3K inhibitor LY294002. Taken together, these results suggest that IFY exerts a protective effect against AD by enhancing the expression levels of anti-apoptosis proteins and reducing the expression levels of pro-apoptosis proteins of B-cell lymphoma-2 (BCL-2) family members though activating the PI3K/AKT pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture. (Pubmed Central) - Feb 20, 2021
Taken together, our data suggest that PLC-γ1 is stimulated in part through EGFR for efficient replication in A549 cells, whereas Akt can be stimulated by virus infection independent of EGFR, and is not essential for virus productive infection, indicating that Akt modulates BoHV-1 replication in a cell type-dependent manner. This study provides novel insights on how BoHV-1 infection activates EGFR signaling transduction to facilitate virus replication.
- |||||||||| Victoza (liraglutide) / Novo Nordisk
Journal: Banxia Xiexin Decoction Ameliorates t-BHP-Induced Apoptosis in Pancreatic Beta Cells by Activating the PI3K/AKT/FOXO1 Signaling Pathway. (Pubmed Central) - Feb 17, 2021
MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis...LY abolished these effects of BXXD. BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Phosphorylated GSK‑3β protects stress‑induced apoptosis of myoblasts via the PI3K/Akt signaling pathway. (Pubmed Central) - Feb 17, 2021
For this purpose, L6 rat myoblasts were cultured under mechanical stimulation and treated with the PI3K kinase inhibitor, LY294002, to elucidate the role of the PI3K/Akt signaling pathway...In addition, the rate of apoptosis in myoblasts subjected to cyclic stretch increased in a time‑dependent manner, peaking at 24 h. Collectively, it was also demonstrated that the PI3K/Akt/GSK‑3β pathway plays an important role in stretch‑induced myoblast apoptosis.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells. (Pubmed Central) - Feb 17, 2021
LY294002 was used to inhibit the activity of PI3K to verify the role of the PI3K/Akt signaling pathway in the restoration of epithelial cell...It was determined that blocking T‑cell immunoglobulin mucin 3 (Tim‑3) signaling in macrophages and PI3K/Akt signaling in epithelial cells eliminated the barrier protection supplied by M2 macrophages. Tim‑3, which maintains macrophage M2 polarization, is a key component of the macrophage‑mediated barrier‑repair process, while M2 macrophages regulate PI3K/Akt signaling in epithelial cells, which in turn enhances pulmonary epithelial barrier function by restoring cell migration.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway. (Pubmed Central) - Feb 17, 2021
Tim‑3, which maintains macrophage M2 polarization, is a key component of the macrophage‑mediated barrier‑repair process, while M2 macrophages regulate PI3K/Akt signaling in epithelial cells, which in turn enhances pulmonary epithelial barrier function by restoring cell migration. The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Rubrofusarin Attenuates Chronic Restraint Stress-Induced Depressive Symptoms. (Pubmed Central) - Feb 13, 2021
Finally, we found that the antidepressant effects of rubrofusarin were blocked by an intracerebroventricular injection of LY294002. These results suggest that rubrofusarin ameliorated CRS-induced depressive symptoms through PI3K/Akt signaling.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Role of up-regulated DDX3 in the proliferation of human cervical cancer cells (Pubmed Central) - Feb 11, 2021
DDX3 overexpression promotes proliferation, migration and invasion of cervical cancer cells, and induces epithelial-mesenchymal transition (EMT). Its mechanism may be related to activation of the PI3K/Akt signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: 1,25(OH)D Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway. (Pubmed Central) - Feb 5, 2021
Western blotting and gelatin zymography were used to detect the expression and activities of VEGF, MMP-2 and MMP-9 secreted by MSCs under the influence of 1,25(OH)D Finally, the VDR antagonist pyridoxal-5-phosphate (P5P) and the PI3K/AKT pathway inhibitor LY294002 were utilized to test the phosphorylation levels of key kinases in the PI3K/AKT pathway by Western blotting and the formation of capillary-like structures in Matrigel...In addition, the ability to form capillary-like structures was reduced when the VDR and PI3K/AKT pathways were blocked. This study confirmed that 1,25(OH)D treatment can strengthen the ability of MSCs to promote vasculogenesis in vitro, and the mechanism may be related to the activation of the PI3K/AKT pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, PARP Biomarker: NCX3 alleviates ethanol-induced apoptosis of SK-N-SH cells via the elimination of intracellular calcium ions. (Pubmed Central) - Feb 2, 2021
The [Ca]i and apoptosis rate of SK-N-SH cells increased 1.31-fold and 1.52-fold after silencing NCX3 compared with those treated with 200 mM EtOH alone for 2 d. In contrast, the [Ca]i and apoptosis rate of SK-N-SH cells decreased 0.26-fold and 0.35-fold after overexpression of NCX3 in the 2 d-200 mM EtOH treatment group. These results suggest that NCX3 plays a critical role in neuronal protection via the elimination of intracellular Ca, which may be a promising target for the prevention and treatment of encephalopathy after ethanol exposure.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, PARP Biomarker: Akt/survivin pathway inhibition enhances the apoptotic cell death-induced by alpha-santalol in human prostate cancer cells. (Pubmed Central) - Jan 28, 2021
Furthermore, inhibition of PI3K-Akt pathway by pharmacological inhibitor, LY294002 enhanced the apoptotic cell death induced by alpha-santalol as determined by cell viability, cellular morphology, active caspase-3 activity and expression of cleaved PARP, cleaved caspase-3 levels. In conclusion, the present study provides novel insight into the molecular circuitry of alpha-santalol-induced cell death and reveals that alpha-santalol targets Akt/Survivin pathway to induce cell death and that the cell death is increased in the presence of a known inhibitor of the pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly, PRI-724 / PRISM Pharma, Ohara Pharma
Journal: The PI3K/AKT pathway promotes fracture healing through its crosstalk with Wnt/β-catenin. (Pubmed Central) - Jan 27, 2021
Notably, the PI3K/AKT pathway is also activated by Wnt3a and is involved in Wnt3a-induced osteoblast proliferation and differentiation. Hence, our results reveal the existence of a Wnt/PI3K/AKT/β-catenin signaling nexus in osteoblasts, highlighting complex crosstalk between PI3K/AKT and Wnt/β-catenin pathways that are critically implicated in fracture healing.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Down-regulation of miRNA-196b expression inhibits the proliferation, migration and invasiveness of HepG2 cells while promoting their apoptosis via the PI3K/Akt signaling pathway. (Pubmed Central) - Jan 23, 2021
The HepG2 cells were also treated with PI3K/Akt signaling pathway inhibitor LY294002, and its effect on cell proliferation, migration, invasion, and apoptosis, and expressions of PIK3, Akt, and p-Akt proteins were determined...Similarly, the protein expressions of PIK3 and p-Akt in the non-treatment group was significantly upregulated, relative to the treatment group (p < 0.05), but there was no significant difference in the expression of Akt protein between the two groups (p > 0.05). Downregulation of miRNA-196b expression inhibits the proliferation, migration and invasiveness of HepG2 cells, while promoting their apoptosis via a mechanism involving the PI3K/Akt signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Hypoglycemic Activity and the Mechanisms of Lycium Bark Extract in db/db Mice. (Pubmed Central) - Jan 23, 2021
Furthermore, LBE increased the glucose uptake, which was measured using C2C12 myotubes, in a concentration-dependent manner, independent of the addition of a phosphatidylinositol 3-kinase inhibitor (i.e., LY294002) and an AMP-activated kinase inhibitor (i.e., dorsomorphin)...These results suggested that LBE decreased the blood glucose level by additive effect such as improvement of the insulin secretion, promoting activity of glucose uptake. These findings suggested that LBE administration can be a novel therapeutic approach for type 2 diabetes.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, Cancer stem cells: PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. (Pubmed Central) - Jan 22, 2021
Pharmacologic inhibition of Akt using LY294002 and Akt1/2 knockdown using shRNA in sarcoma CSCs decreased Nanog expression and spheroid formation and reversed chemotherapy resistance...Finally, in a human sarcoma tumor microarray, expression of CD133, Nanog, and phospho-Akt were 1.8- to 6.8-fold higher in tumor tissue compared with normal tissue. Together, these results indicate that the Akt1/2-Nanog pathway is critical for maintenance of sarcoma CSCs and spheroid-forming cells, supporting further exploration of this pathway as a therapeutic target in sarcoma.
- |||||||||| MK-2206 / Merck (MSD), quercetin (LY294002) / Eli Lilly
Journal, IO biomarker: Cytoprotective effects evaluation of A novel danshensu derivative DEX-018 against oxidative stress injury in HUVECs. (Pubmed Central) - Jan 16, 2021
Compared with DEX-018 alone, MK2206 or LY294002 significantly decreased cell viability of HUVECs, indicating that the protective effect of DEX-018 against t-BHP induced oxidative injury was significantly weakened. It was further verified that the antioxidant and anti-apoptotic effects of DEX-018 were partly related to the phosphadylinositol 3-kinase (PI3K)/Akt signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Siniperca chuatsi rhabdovirus (SCRV) induces autophagy via PI3K/Akt-mTOR pathway in CPB cells. (Pubmed Central) - Jan 16, 2021
SCRV-N mRNA and protein level were decreased by inhibiting PI3K with LY294002, but increased by activating PI3K with 740Y-P. Those results indicated that SCRV infection induced autophagy via the PI3K/Akt-mTOR signal pathway, which will provide new insights into SCRV pathogenesis and antiviral treatment strategies.
- |||||||||| cisplatin / Generic mfg.
Journal: Human RECQL5 promotes metastasis and resistance to cisplatin in non-small cell lung cancer. (Pubmed Central) - Jan 15, 2021
Moreover, knockdown of RECQL5 increased the apoptosis of cisplatin-resistant A549 cell line (A549/DDP) caused by cisplatin treatment. In summary, RECQL5 contributed to the metastasis of NSCLC and assisted NSCLC cells incompletely response to cisplatin therapy, and could be considered as a biomarker or clinical target for NSCLC.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Journal: AKT drives sustained motility following MEK inhibition via promoting SNAIL and AXL in MDA-MB-231 LM2. (Pubmed Central) - Jan 14, 2021
These results suggest that SNAIL and AXL are key factors mediating sustained motility of LM2 cells following MEK suppression. Because AKT mediates motile behavior under MEK suppression, our results suggest that AKT and AXL may be targeted to overcome resistance against drugs targeting the Ras/ERK pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: The effect of astaxanthin on inflammation in hyperosmolarity of experimental dry eye model in vitro and in vivo. (Pubmed Central) - Jan 14, 2021
Moreover, Pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.
- |||||||||| quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal: Zn and mPTP mediate resveratrol-induced myocardial protection from endoplasmic reticulum stress. (Pubmed Central) - Jan 13, 2021
The AKT inhibitor LY294002 and siRNA did not alter the action of resveratrol...Resveratrol prevented 2-DG-induced mPTP opening and increased intracellular Zn2+ concentration indicated by TMRE and Newport Green DCF fluorescence intensity, which were further abrogated by ERK/GSK-3β inhibitors and siRNAs. Our data suggested that resveratrol protected cardiac cells from ERS by mobilizing intracellular Zn2+ and preventing mPTP opening through the ERK/GSK-3β but not PI3K/AKT signaling pathway.
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