- |||||||||| Journal: Molecular basis of V-ATPase inhibition by bafilomycin A1. (Pubmed Central) - Apr 7, 2021
One bafilomycin A1 molecule engages with two c subunits and disrupts the interactions between the c-ring and subunit a, thereby preventing proton translocation. Structural and sequence analyses demonstrate that the bafilomycin A1-binding residues are conserved in yeast and mammalian species and the 7'-hydroxyl group of bafilomycin A1 acts as a unique feature recognized by subunit c.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway (Pubmed Central) - Apr 7, 2021
Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot...UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: Effect of eye acupuncture on autophagy in brain tissue of rats with cerebral ischemia-reperfusion injury (Pubmed Central) - Apr 7, 2021
In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity. Eye acupuncture can improve the neurological function of rats with cerebral ischemia-reperfusion injury, which may be related to accelerating cerebral blood flow and inhibiting autophagy in the ischemic brain.
- |||||||||| Journal: Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival. (Pubmed Central) - Apr 7, 2021
Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.
- |||||||||| Preclinical, Journal, Combination therapy: Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines. (Pubmed Central) - Apr 7, 2021
Collectively, G/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of As and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of As, gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma.
- |||||||||| paclitaxel / Generic mfg.
Journal: Erb-b2 Receptor Tyrosine Kinase 2 (ERBB2) Promotes ATG12-Dependent Autophagy Contributing to Treatment Resistance of Breast Cancer Cells. (Pubmed Central) - Apr 7, 2021
We clarify that lapatinib, a dual inhibitor for EGFR and ERBB2, promoted autophagy in cells expressing only EGFR but inhibited autophagy in cells expressing only ERBB2...Finally, ERBB2 antibody treatment led to reduced expression of ATG12 and autophagy inhibition increasing drug or starvation-induced cell death in ERBB2-positive breast cancer cells. Taken together, this study provides a novel approach for the treatment of ERBB2-positive breast cancer by targeting ATG12-dependent autophagy.
- |||||||||| Journal: Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis. (Pubmed Central) - Apr 7, 2021
The expressions of LC3, Beclin1, p62, and autophagy-related 5-12 (Atg5-12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group.
- |||||||||| tamoxifen / Generic mfg.
Journal: Autophagy Triggers Tamoxifen Resistance in Human Breast Cancer Cells by Preventing Drug-Induced Lysosomal Damage. (Pubmed Central) - Apr 7, 2021
Consistently, we also demonstrate that other breast cancer cells that overexpress selected mRNAs encoding iron-binding proteins are less sensitive to Tam-induced lysosomal damage when autophagy is activated. Collectively, our data demonstrate that autophagy triggers Tam resistance in breast cancer cells by favoring the lysosomal relocation of overexpressed factors that restrain tamoxifen-induced lysosomal damage.
- |||||||||| Journal: Effect of Autophagy to Drug Resistance of B-cell Lymphoma Cells (Pubmed Central) - Apr 7, 2021
Collectively, our data demonstrate that autophagy triggers Tam resistance in breast cancer cells by favoring the lysosomal relocation of overexpressed factors that restrain tamoxifen-induced lysosomal damage. The higher autophagy activity in lymphoma cells, the lower chemotherapy resistance of the lymphoma cells after autophagy was inhibited.
- |||||||||| Journal: Autophagy proteins and its homeostasis in cellular environment. (Pubmed Central) - Apr 2, 2021
TLR2/6 mediated signaling stimulated by LPG produces many pro-inflammatory cytokines like IL12, TNFα and IL6 etc. Among them TNFα, causes the activation of PI3P through a series of events, which results in activation of autophagic machinery, whereas, IL10 through ATG9 and mTOR activation, inhibits autophagy. The mathematical modeling of these pathways shows that, ATG9-PI3P act as a negative feedback loop in autophagic machinery of leishmaniasis.
- |||||||||| sirolimus / Generic mfg.
Journal: CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade. (Pubmed Central) - Apr 1, 2021
Moreover, rapamycin, an autophagy activator, did not rescue myotube atrophy or apoptosis induced by NNC-55, and the autophagy inhibitors 3-MA and HCQ accelerated this damage...Finally, we found multisite muscle atrophy and decreased muscle function in Cacna1h (TH-null) mice, as well as increased autophagy inhibition and apoptotic signals in the PFM of old WT mice after MVD and TH-null mice. Taken together, our results suggest that MVD-associated PFD is partially attributed to CACNA1H downregulation-induced PFM atrophy and that ERS is a potential therapeutic target for this disease.
- |||||||||| Journal: Salmonella Enteritidis Effector AvrA Suppresses Autophagy by Reducing Beclin-1 Protein. (Pubmed Central) - Apr 1, 2021
In organoids and infected mice, we explored the physiologically related effects and mechanism of AvrA in reducing Beclin-1 through the JNK pathway, thus attenuating autophagic responses. This finding not only indicates an important role of S. Enteritidis effector in reducing host protein as a strategy to suppress autophagy, but also suggests manipulating autophagy as a new strategy to treat infectious diseases.
- |||||||||| sirolimus / Generic mfg.
Journal: Phenotyping reveals the targets of a pseudo-natural product autophagy inhibitor. (Pubmed Central) - Mar 30, 2021
Exploration of indocinchona alkaloid bioactivity in phenotypic assays revealed a novel class of azaindole-containing autophagy inhibitors, the 'azaquindoles'. Subsequent characterisation of the most potent compound, azaquindole-1, in the morphological "cell painting" assay, guided target identification efforts which revealed that, in contrast to the parent Cinchona alkaloids, azaquindoles selectively inhibit starvation- and rapamycin-induced autophagy by targeting the lipid kinase VPS34.
- |||||||||| metformin / Generic mfg.
Clinical, Journal, IO biomarker: The Protective Role of Metformin in Autophagic Status in Peripheral Blood Mononuclear Cells of Type Two Diabetic Patients. (Pubmed Central) - Mar 30, 2021
Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in type 2 diabetes is associated with the fusion process of lysosomes which could be overcome by metformin.
- |||||||||| Journal, IO biomarker: Differential expression of MAGEA6 toggles autophagy to promote pancreatic cancer progression. (Pubmed Central) - Mar 30, 2021
Using xenograft mouse models, we demonstrated that inhibition of autophagy is critical for tumor initiation whereas reinstitution of autophagy as a consequence of MAGEA6 degradation contributes to tumor progression. These findings could inform cancer immunotherapeutic strategies for targeting MAGEA antigens and provide mechanistic insight into the divergent roles of MAGEA6 during pancreatic cancer initiation and progression.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signaling. (Pubmed Central) - Mar 30, 2021
However, there are differences in responses to these agents, for instance, in their abilities to upregulate direct targets of transcription factor EB (TFEB), a substrate of mTORC1 that drives transcription of many lysosomal and autophagy-related genes. Nonetheless, our data imply that widely used agents that alkalinise intralysosomal pH are mimetics of acute lysosomal storage disorders and emphasise the importance of considering the result of CQ and BafA on mTORC1 signaling when interpreting the effects of these agents on cellular physiology.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy. (Pubmed Central) - Mar 30, 2021
In in vitro experiments and in xenografts, depletion of TRPM2 in AML inhibited leukemia proliferation, and doxorubicin sensitivity was increased...These data show that TRPM2 has an important role in AML proliferation and survival through regulation of key transcription factors and target genes involved in mitochondrial function, bioenergetics, the antioxidant response, and autophagy. Targeting TRPM2 may represent a novel therapeutic approach to inhibit myeloid leukemia growth and enhance susceptibility to chemotherapeutic agents through multiple pathways.
- |||||||||| sirolimus / Generic mfg.
Journal: The Protective Effects of Melatonin Against LPS-Induced Septic Myocardial Injury: A Potential Role of AMPK-Mediated Autophagy. (Pubmed Central) - Mar 30, 2021
To confirm whether the protection of melatonin was mediated by AMPK and autophagy, Compound C, an AMPK inhibitor; 3-MA, an autophagy inhibitor; and Rapamycin (Rapa), an autophagy activator, were used in this study...In addition, in vitro studies further confirmed the protection of melatonin against LPS-induced myocardial injury and the mechanisms involving AMPK-mediated autophagy signaling. In summary, our results demonstrated that melatonin protects against LPS-induced septic myocardial injury by activating AMPK mediated autophagy pathway.
- |||||||||| Journal: ATG16L1 autophagy pathway regulates BAX protein levels and programmed cell death. (Pubmed Central) - Mar 30, 2021
Co-immunoprecipitation analyses demonstrated that SNAP23 and ATG16L1 proteins form a stable complex independent of nutrient condition, while in the nutrient-deplete state BAX binds to SNAP23 to form a ternary BAX/SNAP23/ATG16L1 protein complex. Taken together, these data support a model in which SNAP23 plays a crucial function as a scaffold for ATG16L1 necessary for the suppression of BAX activation and induction of the intrinsic cell death program.
- |||||||||| Preclinical, Journal: Sodium orthovanadate inhibits growth of acute leukemia HL60 cells and HL60/A cells In vitro. (Pubmed Central) - Mar 30, 2021
In this study, for the first time, we found that SOV could inhibit proliferation, induce G2/M cell cycle arrest and apoptosis, and could inhibit autophagy of acute leukemia cell lines in vitro. Thus, our findings suggest that SOV could effectively suppress the growth of acute leukemia HL60 cells and HL60/A cells through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in acute promyelocytic leukemia treatment.
- |||||||||| [VIRTUAL] Stapled peptide inhibitors of Atg8 proteins () - Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_6336;
These peptides include the highest-affinity LC3B-selective ligands reported to date and provide novel information on the structural determinants of selectivity for Atg8 proteins. Our designs will be useful tools for understanding the role of individual Atg8 proteins in autophagy and in cancer.Amino acids in the 3rd, 4th, 5th, and 8th positions of the K1 peptide were replaced with thiol-containing residues and joined by xylene linkers to create (i,i+3), (i,i+4), and (i,i+5) stapled peptide inhibitors of GABARAP.
- |||||||||| [VIRTUAL] AMYLOIDOGENIC LIGHT CHAIN ENDOCYTOSIS IN RENAL PROXIMAL TUBULAR CELLS LEADS TO IMPAIRED AUTOPHAGY () - Mar 27, 2021 - Abstract #ISOA2020ISOA_56;
Our designs will be useful tools for understanding the role of individual Atg8 proteins in autophagy and in cancer.Amino acids in the 3rd, 4th, 5th, and 8th positions of the K1 peptide were replaced with thiol-containing residues and joined by xylene linkers to create (i,i+3), (i,i+4), and (i,i+5) stapled peptide inhibitors of GABARAP. Dysfunctional autophagy and mitophagy caused by direct cellular toxicity of BJPs likely contribute to tubular cell toxicity in AL amyloidosis but the extent of inhibition does not seem to correlate with in vitro stability of BJPs assessed by limited proteolysis at neutral pH.
- |||||||||| Journal: α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation. (Pubmed Central) - Mar 27, 2021
High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.
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