- |||||||||| Journal: Chlorogenic Acid Alleviates Aβ-Induced Autophagy and Cognitive Impairment via the mTOR/TFEB Signaling Pathway. (Pubmed Central) - Mar 16, 2021
Further analysis showed that CGA markedly promoted lysosomal activity, and this was accompanied by upregulated cathepsin D protein expression, which was induced by the mTOR/TFEB signaling pathway in APP/PS1 mice and Aβ-exposed SH-SY5Y cells (P<0.05). CGA treatment restored autophagic flux in the brain and alleviated cognitive impairments in APP/PS1 mice via enhanced activation of the mTOR/TFEB signaling pathway.
- |||||||||| Journal: Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy. (Pubmed Central) - Mar 16, 2021
Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.
- |||||||||| Journal: Gene and protein expression of mTOR and LC3 in hepatocellular carcinoma, colorectal liver metastasis and "normal" liver tissues. (Pubmed Central) - Mar 16, 2021
the different expression of proteins considered, owning their interaction and diverse tissue microenvironment, indicate an impairment of the autophagy flux in primary liver tumors that is critical for the promotion of tumorigenesis process and a coexistence of autophagy inhibition and activation mechanisms in secondary liver tumors. Differences in mTOR and LC3 transcripts emerged in tumor-free tissues, therefore particular attention should be considered in selecting the control group.
- |||||||||| Review, Journal: Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies. (Pubmed Central) - Mar 16, 2021
In this review, we will summarize our current knowledge of the impact of genetically and pharmacologically modulating autophagy genes and proteins, involved in the different steps of the autophagy process, on the therapeutic benefit of various cancer therapies. We will also briefly discuss the challenges and limitations to developing potent and selective autophagy inhibitors that could be used in ongoing clinical trials.
- |||||||||| chlorpromazine / Generic mfg.
[VIRTUAL] MOLECULAR MECHANISM OF AUTOPHAGY MEDIATED CLAUDIN-2 ENDOCYTOSIS VIA AP2M1 (DDW Virtual) - Mar 15, 2021 - Abstract #DDW2021DDW_1282; Bafilomycin (autophagy inhibitor) and chlorpromazine (clathrin endocytosis inhibitor), individually, prevented starvation-induced reduction in claudin-2 levels in Caco-2 cells, suggesting an important role of autophagy and clathrin mediated endocytosis in claudin-2 reduction... Our study suggests that autophagy enhances intestinal epithelial TJ barrier by degradation of pore-forming TJ protein claudin-2 via ATG7, AP2M1 associated clathrin endocytosis.
- |||||||||| gemcitabine / Generic mfg.
[VIRTUAL] Novel autophagy inhibitor to treat pancreatic cancer () - Mar 13, 2021 - Abstract #AACR2021AACR_4631; Additionally, the compound has shown synergy with the current standard of care chemotherapeutic, gemcitabine, with an 88.9% reduction in tumor volume in the combination of the two drugs compared to gemcitabine treated alone (p<0.0001) in two separate treatment regimens using a pancreatic PDX mouse model...The drug treatment also promotes a decrease in pluripotency markers, particularly in Sox2 levels. Finally, the drug is well-tolerated with a maximum tolerated dose above 100 mg/kg in mice and is orally bioavailable.
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Journal: Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators. (Pubmed Central) - Mar 13, 2021 Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-MA) or an autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment for 2, 4, and 6 hr in vitro...These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia-reperfusion injury.
- |||||||||| Clinical, Journal: Asessing Tissue-Specific Autophagy Flux in Adult Caenorhabditis elegans. (Pubmed Central) - Mar 13, 2021
Here we describe a method for assessing autophagic flux in multiple tissues of C. elegans by quantifying the pool of autophagic vesicles using fluorescently labelled Atg8/LGG-1 reporters upon autophagy inhibition using bafilomycin A (BafA). This methodology has revealed that autophagic activity varies in different cell types of C. elegans during aging.
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Journal: Autophagy Suppresses Toll-Like Receptor 3-Mediated Inflammatory Reaction in Human Epidermal Keratinocytes. (Pubmed Central) - Mar 13, 2021 Rapamycin-induced activation of autophagy significantly reduced poly (I:C)-induced inflammatory reaction, whereas, inhibition of autophagy by 3-methyladeine increased that. Our results indicate that the induction of autophagy may attenuate TLR3-mediated immune responses in human epidermal keratinocytes, thus providing novel insights into the mechanisms underlying the development of inflammatory skin diseases including psoriasis.
- |||||||||| Preclinical, Journal: In Vivo Suppression of Autophagy via Lentiviral shRNA Targeting Atg5 Improves Lupus-Like Syndrome. (Pubmed Central) - Mar 13, 2021
The mice treated with shAtg5-lentivirus exhibited lower levels of proteinuria, serum anti-dsDNA antibody, B-cell activating factor (BAFF), and glomerular immune complex deposition. Therefore, targeting autophagy to moderate overactivated autophagy in immune cells seems to be a novel strategy for combination therapy of lupus.
- |||||||||| MK-2206 / Merck (MSD)
Journal: Stigmasterol Simultaneously Induces Apoptosis and Protective Autophagy by Inhibiting Akt/mTOR Pathway in Gastric Cancer Cells. (Pubmed Central) - Mar 13, 2021 The pretreatment with the Akt inhibitor MK-2206 could promote apoptosis and autophagy induced by SS, predicting that Akt/mTOR pathway is involved in SS-induced apoptosis and autophagy...Finally, an in vivo study demonstrated that tumor growth of gastric cancer was suppressed by SS in a xenograft model. Our findings illustrate for the first time that SS simultaneously induces apoptosis and protective autophagy by inhibiting Akt/mTOR pathway in gastric cancer cells, and SS may become a potential anticancer drug in treating gastric cancer in the future.
- |||||||||| Journal: Aggravated ulcerative colitis caused by intestinal Metrnl deficiency is associated with reduced autophagy in epithelial cells. (Pubmed Central) - Mar 12, 2021
The autophagy-related AMPK-mTOR-p70S6K pathway was also activated in DSS-induced colitis, and this pathway was partially blocked by intestinal epithelial Metrnl deficiency, as indicated by a decrease in AMPK phosphorylation and an increase in mTOR and p70S6K phosphorylation in DSS-treated Metrnl mice compared with WT mice. Therefore, Metrnl deficiency deteriorated ulcerative colitis at least partially through inhibition of autophagy via the AMPK-mTOR-p70S6K pathway, suggesting that Metrnl is a therapeutic target for ulcerative colitis.
- |||||||||| sirolimus / Generic mfg.
Journal: VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1. (Pubmed Central) - Mar 12, 2021 VEGF-induced autophagy is transient and probably terminated by mechanistic target of rapamycin (mTOR), which is activated by VEGF in a delayed manner...In line with this, inhibition of autophagy impaired VEGF-mediated formation of the Notch intracellular domain, a critical regulator of angiogenesis. Our study characterizes autophagy induction as a pro-angiogenic function of the VEGF/AMPK pathway and suggests that timely activation of autophagy-initiating pathways may help to initiate angiogenesis.
- |||||||||| Torisel (temsirolimus) / Pfizer
[VIRTUAL] mTOR inhibitor induces non-apoptotic, autophagy dependent cell death (ADCD) in TP53 mutant HNSCC () - Mar 11, 2021 - Abstract #AACR2021AACR_2878; We investigated the mechanism by which the mTOR inhibitor CCI-779 inhibits cell growth of TP53 mutant HNSCC in vitro...This is a novel mechanism of how rapalogues induce ADCD through the stabilization/ activation of ULK1 in HPV-negative TP53 mutant HNSCC cells. Together these data highlight the importance of how mTORi can be used to accelerate tumor cell death in HPV-negative TP53 mutant HNSCC.
- |||||||||| ONC212 / Oncoceutics
[VIRTUAL] Combination therapy with MEK inhibitors and a novel anti-neoplastic drug, imipridone ONC212, demonstrates synergy in pancreatic ductal adenocarcinoma cell lines () - Mar 11, 2021 - Abstract #AACR2021AACR_2869; Autophagy, a catabolic process used by many tumors to maintain viability, can be targeted with various agents such has hydroxychloroquine and chloroquine, and recent preclinical data has shown that the combination of these agents with inhibitors of MEK/ERK can synergistically induce cell death...In conclusion, the combination of trametinib and ONC212 produces a synergistic cytotoxic effect on tumor cells at doses that are non-toxic to normal cells...Similar synergistic effects were noted in a KRAS wild-type pancreatic cancer cell lines, suggesting an autophagy-independent mechanism. Thus, this combination may represent a potential therapeutic modality for PDAC.
- |||||||||| dasatinib / Generic mfg.
[VIRTUAL] Nedd9 controls autophagy to limit non-small cell lung cancer (NSCLC) growth () - Mar 11, 2021 - Abstract #AACR2021AACR_1078; Treatment of mice with the Src inhibitor dasatinib significantly reduced, but did not eliminate, tumor growth in KP and KPN mice...In vivo treatment of KPN and KP mice with the autophagy inhibitor chloroquine completely eliminated the growth advantage of KPN tumors, emphasizing the importance of autophagy for the growth differential. In sum, these data for the first time identify and define a previously unknown role for the pro-metastatic protein NEDD9 in control of autophagy, based on a role as a negative regulator of the Lkb1-Ampk signaling axis in NSCLC.
- |||||||||| Journal: Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition. (Pubmed Central) - Mar 11, 2021
Furthermore, co-immunoprecipitation and immunofluorescence double staining suggested that there were no direct interactions between Mst1 and Lin28a. Lin28a increased the expression of Akt, which inhibited the activation of Mst1-mediated apoptotic pathways.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy. (Pubmed Central) - Mar 11, 2021 The proteasome inhibitor MG132 and the autophagy inhibitor bafilomycin A1 were found to upregulate the PDCD4 levels...In ATG (autophagy related) 5-deficient Huh7 cells in which autophagy was impaired, the PDCD4 levels were increased at the basal levels and upregulated in the presence of autophagy inhibitors. Based on the above findings, we concluded that after phosphorylation in the degron and ubiquitination, PDCD4 is degraded by both the proteasome and autophagy systems.
- |||||||||| Journal: Cadmium induces cell growth in A549 and HELF cells via autophagy-dependent glycolysis. (Pubmed Central) - Mar 11, 2021
Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.
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