- |||||||||| 5-fluorouracil / Generic mfg.
Journal: S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation. (Pubmed Central) - Oct 22, 2021
We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.
- |||||||||| Journal: Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. (Pubmed Central) - Oct 20, 2021
We further identified capping protein Zβ (CapZβ) as a V1 binding protein and showed that it is required for the V1-mediated inhibition of migration and metastasis of cancer cells. Collectively, our results indicate that V1 targets CapZβ to inhibit endosomal trafficking and metastasis.
- |||||||||| Review, Journal: Mechanisms and Therapeutic Implications of GSK-3 in Treating Neurodegeneration. (Pubmed Central) - Oct 20, 2021
In this review, we focus on three pathways that represent prominent mechanisms linking GSK-3 with neurodegenerative disorders: cytoskeleton organization, the mammalian target of rapamycin (mTOR)/autophagy axis, and mitochondria. We also consider the challenges and opportunities in the development of GSK-3 inhibitors for treating neurodegeneration.
- |||||||||| tamoxifen / Generic mfg.
Journal: DDRGK1, a crucial player of ufmylation system, is indispensable for autophagic degradation by regulating lysosomal function. (Pubmed Central) - Oct 20, 2021
To explore the regulation mechanism of DDRGK1 on autophagy, in this study, we established an immortalized mouse embryonic fibroblast (MEF) cell lines harvested from the DDRGK1:ROSA26-CreERT2 mice, in which DDRGK1 depletion can be induced by 4-hydroxytamoxifen (4-OHT) treatment...Hence, this study confirms a crucial role of DDRGK1 as an autophagy regulator by controlling lysosomal function. It may provide a theoretical basis for the treatment strategies of various physiological diseases caused by DDRGK1 deficiency.
- |||||||||| Journal: PXDN reduces autophagic flux in insulin-resistant cardiomyocytes via modulating FoxO1. (Pubmed Central) - Oct 20, 2021
Thus, we come to conclusion that PXDN plays a key role in PA-induced cell death by impairing autophagic flux through inhibiting FoxO1, and FoxO1 may also affect the expression of PXDN. These findings may develop better understanding of potential mechanisms regarding autophagy in insulin-resistant cardiomyocytes.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: The therapeutic effect of TBK1 in intervertebral disc degeneration via coordinating selective autophagy and autophagic functions. (Pubmed Central) - Oct 20, 2021
These functions of TBK1 were abolished by chloroquine-medicated autophagy inhibition.P-TBK1, an activation form of TBK, is involved in selective autophagy through directly phosphorylating P62 at Ser 403, and the activation of TBK1 is also dependent on Parkin manner...We demonstrated that TBK1 overexpression attenuated senescence and apoptosis and promoted NPCs survival via upregulating autophagy. TBK1 represents a promising avenue for IVDD treatment.
- |||||||||| SP600125 / BMS
Journal: Neohesperidin Induces Cell Cycle Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells. (Pubmed Central) - Oct 20, 2021
Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.
- |||||||||| GSK2606414 / GSK, Institute of Cancer Research, Dartmouth College
Journal: Nox4 Promotes RANKL-Induced Autophagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway. (Pubmed Central) - Oct 20, 2021
Blocking the activation of PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS scavenger (NAC) or PERK inhibitor (GSK2606414) significantly inhibited autophagy during RANKL-induced osteoclastogenesis. Collectively, this study reveals that Nox4 promotes RANKL-induced autophagy and osteoclastogenesis via activating ROS/PERK/eIF-2α/ATF4 pathway, suggesting that the pathway may be a novel potential therapeutic target for osteoclastogenesis-related disease.
- |||||||||| hydroxychloroquine / Generic mfg.
[VIRTUAL] The Emerging Role of the mTORC2/Rictor Signaling Complex in Autophagy Dysregulation-Associated Diabetic Kidney Disease () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_2013;
The effect of autophagy was further highlighted in control mice treated with the autophagy inhibitor hydroxychloroquine, that mirrored the effect of diabetes on functional, phenotypic, histological, and molecular changes in the kidney...More importantly, JR treatment regulated diabetes-induced autophagy protein dysregulation (Beclin, Atg3, and LC3). Conclusion Our data suggest that targeting mTORC2 signaling could be a potential therapeutic target for DKD.
- |||||||||| [VIRTUAL] Autophagy Deficiency in Urothelial Cells Activates Progressive NF-κB Signaling () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1945;
Under these conditions, non-canonical NF-κB mediators TWEAK and its receptor Fn14 were highly responsive. Further investigation of this progressive NF-κB signaling series in urothelial cells may be critical for understanding the etiology of COU and any lingering chronic response after COU is resolved.
- |||||||||| chloroquine phosphate / Generic mfg., deoxyglucose / Generic mfg.
[VIRTUAL] Autophagy Inhibition Ameliorates Polycystic Kidney Disease () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1861;
Double Pkd1 Atg7 KO mice had significantly lower kidney weight than single Pkd1 KO mice. Both pharmacological and genetic autophagy inhibition resulted in less PKD.
- |||||||||| sirolimus / Generic mfg.
Journal: γ-d-Glutamyl-meso-diaminopimelic acid induces autophagy in bovine hepatocytes during nucleotide-binding oligomerization domain 1-mediated inflammation. (Pubmed Central) - Oct 16, 2021
To achieve this aim, hepatocytes separated from cows at ∼160 days in milk (DIM) were divided into six groups: the nontreated control (CON) group, the rapamycin-treated (RAP) group as a positive control, the iE-DAP-treated (DAP) group, the 3-MA-treated (MA) group, the rapamycin with 3-MA (RM) group, and the iE-DAP with 3-MA (DM) group...The application of the autophagy inhibitor increased the expression of inflammatory molecules and alleviated autophagy-associated molecules. Taken together, these findings suggest that NOD1 is a key player for regulating both ATG16L1 and RIPK2-ULK1 directed autophagy during inflammation in response to iE-DAP in bovine hepatocytes.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: YAP promotes autophagy and progression of gliomas via upregulating HMGB1. (Pubmed Central) - Oct 16, 2021
YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.
- |||||||||| Journal, IO biomarker: YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression. (Pubmed Central) - Oct 16, 2021
Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.
- |||||||||| Journal: Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis. (Pubmed Central) - Oct 16, 2021
Furthermore, NF-κBp65 in hepatocytes repressed PUMA-mediated hepatocytes apoptosis via regulating the Bcl-2 family, while NF-κBp65 deficiency in hepatocytes promoted PUMA-mediated hepatocytes apoptosis and enhanced apoptosis-linked inflammatory response, which contributed to the activation of HSCs and liver fibrogenesis. These results suggest that Fas/FasL contributes to NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to enhance liver fibrogenesis, and this network could be a potential therapeutic target for liver fibrosis.
- |||||||||| Journal: Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy. (Pubmed Central) - Oct 16, 2021
More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.
- |||||||||| Review, Journal: Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics. (Pubmed Central) - Oct 16, 2021
Recently, some anticancer lysosomotropic drugs (eg, nortriptyline, siramesine, desipramine) and their nanoformulations have been engineered to specifically accumulate within these organelles...Other anticancer drugs like doxorubicin, quinacrine, chloroquine and DQ661 have also been used which act through multi-target points...The anticancer applications of these nanoformulations have led them up to various stages of clinical trials. Here in this review article, we present the recent updates about the lysosome ultrastructure, its cross-talk with other organelles, and the novel strategies of targeting this organelle in tumor cells as a recent innovative approach of cancer management.
- |||||||||| methimazole / Generic mfg.
Preclinical, Journal: Hypothyroidism Induces Interleukin-1-Dependent Autophagy Mechanism as a Key Mediator of Hippocampal Neuronal Apoptosis and Cognitive Decline in Postnatal Rats. (Pubmed Central) - Oct 15, 2021
Therefore, we used a rat model of developmental hypothyroidism, generated through methimazole treatment from gestation until young adulthood...We further related these molecular results with cognition through Y-maze and passive avoidance tests, demonstrating an IL-1Ra and 3-methyladenine-mediated improvement in learning-memory performances of the hypothyroid rats. Taken together, our study enlightens the critical role of neuroinflammation-dependent autophagy mechanism in TH-regulated hippocampal functions, disrupted in developmental hypothyroidism.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: Assessing methods to quantitatively validate TGFβ-dependent autophagy. (Pubmed Central) - Oct 15, 2021
Finally, we demonstrated that ATG5 and ATG7 are critical for TGFβ-dependent autophagy in NSCLC cells. The application of this model will fuel future experiments to characterize TGFβ-dependent autophagy, which is necessary to understand the molecular processes that link, TGFβ, autophagy and tumorigenesis.
- |||||||||| Review, Journal: Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update. (Pubmed Central) - Oct 14, 2021
Furthermore, some of the phytochemicals are effective against more than one cancer type. Therefore, understanding these mechanisms provides paths for future formulation of novel anticancer drugs, as well as highlighting potential areas of research.
- |||||||||| Review, Journal: Glycolysis-induced drug resistance in tumors-A response to danger signals? (Pubmed Central) - Oct 14, 2021
We also discern similarities between changes occurring in tumor cells in response to stimuli inducing glycolysis-associated drug resistance and those occurring in cells of the innate immune system in response to danger signals and that have been referred to as danger-associated metabolic modifications. Eventually, we briefly address that also mitochondrial oxidative metabolism may induce drug resistance and discuss the therapeutic implications deriving from the fact that the main energy-generating metabolic pathways may be both at the origin of antitumor drug resistance.
- |||||||||| hydroxychloroquine / Generic mfg.
Journal, IO biomarker: Malignant pleural mesothelioma co-opts BCL-X and autophagy to escape apoptosis. (Pubmed Central) - Oct 14, 2021
Importantly, BCL-X inhibition elicits protective autophagy, and concomitant blockade of BCL-X and autophagic machinery with A-1155463 and hydroxychloroquine (HCQ), the US Food and Drug Administration (FDA)-approved autophagy inhibitor, synergistically enhances anti-MPM effects in vitro and in vivo. Together, our work delineates the molecular basis underlying resistance to apoptosis and uncovers an evasive mechanism that limits response to BH3 mimetics in MPM, suggesting a novel strategy to target this aggressive disease.
- |||||||||| RapaLink-1 / University of California, Revolution Medicines
Journal: Rapalink-1 and Hydroxychloroquine Exhibit an Additive Effect in Undifferentiated Pleomorphic Sarcoma by Inducing Apoptosis. (Pubmed Central) - Oct 14, 2021
These findings not only improve our understanding of the mechanism underlying SARS-CoV-2 infection-induced pathogenic inflammation but also have important implications for developing anti-inflammatory therapies, such as ROS and autophagy inhibitors, for COVID-19 patients. Combined treatment with Rapalink-1 and hydroxychloroquine may be used as a potential therapeutic agent against UPS.
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