- |||||||||| quercetin (LY294002) / Eli Lilly, SP600125 / Celgene
Mechanisms underlying human placental CD34+-derived natural killer cell cytotoxicity against glioblastoma (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_566;
Our results demonstrate the importance of PI3K and JNK pathways in mediating PNK cytotoxicity to GBM cell line targets. These data combined with our receptor profiling on PNK cells establish the rationale for further investigating receptor-ligand interactions that directly modulate PI3K and JNK activity.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega, SP600125 / Celgene
Journal: Myricetin treatment induces apoptosis in canine osteosarcoma cells by inducing DNA fragmentation, disrupting redox homeostasis, and mediating loss of mitochondrial membrane potential. (Pubmed Central) - Oct 2, 2019
Moreover, inhibition of PI3K and MAPK using LY294002, U0126, or SP600125, in addition to myricetin treatment, effectively suppressed cell proliferation compared to treatment with myricetin or each inhibitor alone. Therefore, we concluded that myricetin may be a potentially effective and less toxic therapeutic agent to prevent and control progression of canine osteosarcoma.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury. (Pubmed Central) - Oct 2, 2019
Collectively, these findings identified that UBIAD1 protects against OGD/R-induced multiple subcellular organelles injury through PI3K/AKT Pathway. These results suggest that apoM possesses protective properties against LPS-induced organ injuries and could potentially be introduced as a novel therapy for the severe conditions that are consequent to sepsis.
- |||||||||| quercetin (LY294002) / Eli Lilly, Miostat (carbachol) / Novartis
Journal: 7,8-Dihydroxyflavone Enhances Cholinergic Contraction of Rat Gastric Smooth Muscle via Augmenting Muscarinic M3 Receptor Expression. (Pubmed Central) - Oct 2, 2019
In this study, we explored how 7,8-DHF affected the carbachol (CCh)-induced contraction of rat gastric muscle by way of measuring the contractile tension of muscular strips...To pursue how 7,8-DHF could augment CCh-activated PLC-γ phosphorylation, we first examined the effect of 7,8-DHF on the expression of muscarinic receptors in gastric muscle and found that 7,8-DHF specifically increased M3 but not M2 receptor expression possibly through TrkB/Akt (protein kinase B) pathway because the Akt antagonist, LY294002 significantly suppressed the 7,8-DHF-augmemted M3 expression and completely blocked the 7,8-DHF-enhanced cholinergic contraction...Rats fed orally with 7,8-DHF exhibited increased gastric emptying rates. These results illustrate the molecular mechanism for 7,8-DHF's effects on gastric dynamics and suggest a role for this drug in enhancing gastric dynamics in specific patient populations.
- |||||||||| tyrphostin (AG 490) / EMD Serono, Yissum Research Development Company, quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Preclinical, Journal: Specific effects of neuregulin-1β on the communication between DRG neurons and skeletal muscle cells in vitro. (Pubmed Central) - Oct 2, 2019
These data imply that NRG-1β is essential for the nerve-muscle communication by enhancing growth and modifying phenotypes of the two different kinds of cells. The specific effects produced by NRG-1β add novel interpretation for nerve-muscle communication between sensory neurons and SKM cells.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega, SP600125 / Celgene
Journal: Sideroxylin (Callistemon lanceolatus) suppressed cell proliferation and increased apoptosis in ovarian cancer cells accompanied by mitochondrial dysfunction, the generation of reactive oxygen species, and an increase of lipid peroxidation. (Pubmed Central) - Sep 28, 2019
Additionally, sideroxylin activated the phosphorylation of ERK1/2, JNK, P38, and MAPK proteins and the use of LY294002, U0126, SB203580, and SP600125 to block their phosphorylation, respectively, in ES2 and OV90 cells. Collectively, the results of present study indicated that sideroxylin was a novel therapeutic agent to combat the proliferation of ovarian cancer cells through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction.
- |||||||||| MK-2206 / Merck (MSD), quercetin (LY294002) / Eli Lilly
Journal: Hexabromocyclododecanes promoted autophagy through the PI3K/Akt/mTOR pathway in L02 cells. (Pubmed Central) - Sep 27, 2019
These results indicated that PI3K/Akt/mTOR pathway was participated in regulating autophagy process promoted by HBCDs. In above, HBCDs could induce mitochondrial-dependent apoptosis and autophagy in L02 cells, which was modulated by PI3K/Akt/mTOR pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis. (Pubmed Central) - Sep 26, 2019
We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002...Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP-13 by activating NF-?B pathway. In conclusion, inhibition of PI3K/AKT/NF-?B axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Dehydroepiandrosterone rehabilitate BRL-3A cells oxidative stress damage induced by hydrogen peroxide. (Pubmed Central) - Sep 26, 2019
However, the rise in PI3K and p-Akt protein levels, and the decrease in Bax and capase-3 protein levels induced by DHEA treatment were reversed when the cells pretreated with LY294002 (PI3K inhibitor)...In addition, DHEA decreased the apoptosis by inhibiting caspase-3 and Bax protein levels and this action mainly achieved via the activation of PI3K/Akt signaling pathways in HO-induced BRL-3A cells. These results provided substantial information for DHEA as a nutritional supplement to treat oxidative stress and it related diseases in animals and humans.
- |||||||||| perifosine (D21266) / AEterna Zentaris, quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Taurine Promotes Neuritic Growth of Dorsal Root Ganglion Cells Exposed to High Glucose in Vitro. (Pubmed Central) - Sep 22, 2019
However, the protective effects of taurine were blocked in the presence of PI3K antagonists LY294002 or Akt antagonists Perifosine. These results indicate that taurine promotes neurite outgrowth of DRG neurons exposed to HG via activating Akt/mTOR signal pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Antifibrotic role of PGC-1α-siRNA against TGF-β1-induced renal interstitial fibrosis. (Pubmed Central) - Sep 18, 2019
These results implicate a role of PGC-1α in renal interstitial fibrosis mediated via the TGFβ-RI, PI3K/Akt, and p38 MAPK pathways. Our findings that PGC-1α-siRNA downregulates fibronectin and type I collagen suggest that it can be used as a novel molecular treatment for renal fibrosis.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Clathrin-mediated endocytosis is involved in uptake and toxicity of silica nanoparticles in Caenohabditis elegans. (Pubmed Central) - Sep 18, 2019
In addition, to confirm the role of endocytosis in the toxicity of SiNPs, reproduction test was conducted using endocytosis defective mutants, such as cav-1, cup-2, and chc-1. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure. (Pubmed Central) - Sep 12, 2019
...Autophagy inhibitor (3-methyladenine, 3-MA), HO-1 inhibitor (zinc protoporphyrin, ZnPP) and PI3K specific inhibitor (LY294002) were employed in the study...During the MSCs treatment, the HO-1 expression was increased, while inhibiting HO-1 attenuated the therapeutic effect of MSCs as well as hepatocyte autophagy. These findings suggested MSCs could alleviate ALF by increasing the HO-1 expression, which played an important role in activating autophagy through PI3K/AKT signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone. (Pubmed Central) - Sep 11, 2019
...In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively...Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Nitric oxide prevents HO-induced apoptosis in SK-N-MC human neuroblastoma cells. (Pubmed Central) - Sep 11, 2019
SNAP induced phosphorylation of Akt and Bad and then increased the interactions between 14-3-3β and p-Bad. These data suggest that the NO suppresses HO-induced SK-N-MC cell apoptosis by suppressing apoptosis signal mediating the interaction between 14-3-3β and Bad phosphorylation via PKG/PI3K/Akt.
- |||||||||| quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal: Hepatoprotective effects of limb ischemic post-conditioning in hepatic ischemic rat model and liver cancer patients via PI3K/ERK pathways. (Pubmed Central) - Sep 11, 2019
Moreover, through 16 cases of hepatocellular carcinoma resections, we found that short-term LIPOC treatment significantly suppressed the elevated alanine aminotransferase, aspartic transaminase, and total bilirubin in the early post-operation of liver resection, and reduced reperfusion injury to the ischemic liver. In summary, our study demonstrates that LIPOC could be an effective method for HIRI in the clinical implementation of liver resection and uncovers the potential mechanism of LIPOC in the protective effects of HIRI.
- |||||||||| chloroquine phosphate / Generic Mfg., quercetin (LY294002) / Eli Lilly
Journal: VDR agonists down regulate PI3K/Akt/mTOR axis and trigger autophagy in Kaposi's sarcoma cells. (Pubmed Central) - Sep 10, 2019
Since increment in autophagosomes not always indicates increment in autophagy activity, we used Chloroquine (CQ, 1 μM), an inhibitor of autophagy flow, to confirm autophagy after both VDR agonists treatment. In conclusion, VDR agonists, 1α,25(OH)D or TX 527, inhibited PI3K/Akt/mTOR axis and induced autophagy in endothelial cells expressing vGPCR by a VDR-dependent mechanism.
- |||||||||| quercetin (LY294002) / Eli Lilly, Sprycel (dasatinib) / BMS, Otsuka, Inhibikase
Journal: TWEAK promotes hepatic stellate cell migration through activating EGFR/Src and PI3K/AKT pathways. (Pubmed Central) - Sep 10, 2019
Inhibition of PI3K/AKT reduced the expression of MMP9 induced by TWEAK. The present study, for the first time, demonstrated that TWEAK promoted HSCs migration through the activation of EGFR/Src and PI3K/AKT pathways, which showed a novel potential mechanism of HSCs migration regulated by TWEAK.
- |||||||||| Byetta (exenatide) / AstraZeneca
Journal: Effects of Exendin-4 on the differentiation of neural stem cells from subventricular zone of adult mice in vitro (Pubmed Central) - Sep 7, 2019
The present study, for the first time, demonstrated that TWEAK promoted HSCs migration through the activation of EGFR/Src and PI3K/AKT pathways, which showed a novel potential mechanism of HSCs migration regulated by TWEAK. Ex-4 promotes the differentiation of NSCs into neurons in SVZ of adult mice through GLP-1R receptor, which may be achieved through PI3K/CREB pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: LINC00462 is involved in high glucose-induced apoptosis of renel tubular epithelial cells via AKT pathway. (Pubmed Central) - Sep 7, 2019
...Moreover, AKT-specific inhibitor LY294002 restored the effect of LINC00462 knockdown on apoptosis...Moreover, AKT-specific inhibitor LY294002 restored the effect of LINC00462 knockdown on apoptosis. In conclusion, our study demonstrated that knockdown of LINC00462 can ameliorate oxidative stress and apoptosis in HG-induced RTEC by activating the AKT pathway, suggesting that knockdown of LINC00462 may provide a potential therapeutic approach for DN.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Mechanisms underlying the vasorelaxant effect of trans-4-methoxy-β-nitrostyrene in the rat mesenteric resistance arteries. (Pubmed Central) - Sep 6, 2019
...This effect was unchanged by indomethacin and atropine but was significantly reduced by endothelium removal, L-NAME, LY294002, glybenclamide, TEA, apamin, TRAM 34, or by the association of apamin and TRAM 34...In conclusion, T4MN induced effective vasorelaxant effects in isolated small resistance arteries from SHRs. This vasorelaxation seems to be mediated partly by an endothelium-dependent mechanism involving activation of Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca influx from the extracellular milieu and IP-sensitive intracellular Ca release as well as activation of potassium channels.
- |||||||||| quercetin (LY294002) / Eli Lilly, CGS 21680 / Novartis, Nouriast (istradefylline) / Kyowa Hakko Kirin
Preclinical, Journal: Neuroprotective effect of pharmacological postconditioning on cerebral ischaemia-reperfusion-induced injury in mice. (Pubmed Central) - Sep 6, 2019
This vasorelaxation seems to be mediated partly by an endothelium-dependent mechanism involving activation of Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca influx from the extracellular milieu and IP-sensitive intracellular Ca release as well as activation of potassium channels. The neuroprotective effects of CGS21680 and SF1670 postconditioning on cerebral ischaemia-reperfusion injury may be due to PI3K/Akt pathway activation.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo. (Pubmed Central) - Sep 6, 2019
LY303511 was developed as a negative control of LY294002 without pan-phosphoinositide 3-kinase (PI3K) inhibition...In zebrafish model, LY303511 inhibits CAL 27-xenografted tumor growth. Therefore, LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal, IO Biomarker: Role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock waves therapy (Pubmed Central) - Sep 5, 2019
Myocardial Bax protein expression was significantly lower in the HF+CSWT group than in the HF group and the HF+CSWT+LY294002 group (all P<0.05), which was significantly higher in the HF+LY294002 group than in the HF group (P<0.05). CSWT improves cardiac function and inhibits cardiomyocyte apoptosis through PI3K/Akt signaling pathways in this rat HF model.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Adiponectin and Serine/Threonine Kinase Akt Modulation by Triiodothyronine and/or LY294002 in 3T3-L1 Adipocytes. (Pubmed Central) - Sep 4, 2019
PI3K pathway inhibition for 1 h and posterior treatment with T3, in LY + T3, reduced the adiponectin level and increased pAKT levels compared to those in LY. T3 stimulated adiponectin levels by PI3K pathway activation and T3 can compensate alteration in the PI3K pathway, because with inhibition of the pathway it is able to maintain the basal levels of adiponectin and pAKT.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Antioxidant effects of ginkgolides and bilobalide against cerebral ischemia injury by activating the Akt/Nrf2 pathway in vitro and in vivo. (Pubmed Central) - Sep 1, 2019
...GB combined with different concentrations of LY294002 (PI3K inhibitor) were administrated to SH-SY5Y cells for 1 h after OGD, and then p-Akt and p-Nrf2 levels were detected by western blot...Compared with GA, GK, and BB, GB exerts the strongest antioxidant stress effects against ischemic stroke. Moreover, ginkgolides and BB upregulated the levels of antioxidant proteins through mediating the Akt/Nrf2 signaling pathway to protect neurons from oxidative stress injury.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Apoptosis-Inducing Effect of Ginsenoside Rh2 on Human Acute T Lymphoblastic Leukemia Jurkat Cells and Its Mechanism (Pubmed Central) - Aug 29, 2019
We demonstrate that matrine inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the potential of matrine as an anti-cancer agent for lung cancer. Rh2 can induce the apoptosis of Jurkat cells in time-dose dependent manner, moreover, Rh2 also can result in an obvious block of Jurkat cells at G0/G1, that may be closely related to a series of apoptotic signaling cascades mediated by Rh2 inhibiting PI3K/AKT pathway.
|
