- |||||||||| Journal: Isoangustone A induces autophagic cell death in colorectal cancer cells by activating AMPK signaling. (Pubmed Central) - Sep 17, 2021
Finally, isoangustone A at a dosage of 10 mg/kg potently activated AMPK and autophagic signaling in and inhibited the growth of SW480 human colorectal xenograft in vivo. Taken together, induction of autophagy through activation of AMPK is an important mechanism by which isoangustone A inhibits tumor growth, and isoangustone A deserves further investigation as a promising anti-cancer agent.
- |||||||||| Journal: Thyroid Hormone Induces Ca-Mediated Mitochondrial Activation in Brown Adipocytes. (Pubmed Central) - Sep 17, 2021
Furthermore, edelfosine, a phospholipase C (PLC) inhibitor, prevented T from acting on [Ca], UCP1 abundance, Ψ, and OCR. We suggest that short-term exposure of T induces UCP1 upregulation and mitochondrial activation due to PLC-mediated [Ca] elevation in brown adipocytes.
- |||||||||| Review, Journal: Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells-Are There New Avenues for Treatment? (Pubmed Central) - Sep 17, 2021
Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled "oxygenate, target, use, and digest". In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Urolithin A, a pomegranate metabolite, protects pancreatic β Cells from apoptosis by activating autophagy. (Pubmed Central) - Sep 16, 2021 The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathological tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity. These findings suggest that urolithin A protects against glucolipotoxicity-induced apoptosis in pancreatic β-cells by inducing activation of autophagy.
- |||||||||| clodronate disodium / Generic mfg.
Journal: Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3. (Pubmed Central) - Sep 16, 2021 To explore the mechanism of the protective effect, the macrophage scavenger clodronate, autophagy inhibitor 3-methyladenine, or gene knockout mouse lines NLR family pyrin domain containing 3 (Nlrp3)-null, nuclear factor-erythroid 2-related factor 2 (Nrf2)-null, liver-specific AMP-activated protein kinase (Ampk)a1 knockout (Ampka1) and liver-specific inhibitor of KB kinase β (Ikkb) knockout (Ikkb) mice were subjected to GalN/LPS-induced FH...In conclusion, WA improves GalN/LPS-induced hepatotoxicity by targeting macrophage partially dependent on NLRP3 antagonism, while largely independent of NRF2 signaling, autophagy induction, and hepatic AMPKα1 and IκκB. These results support the concept of treating FH by pharmacologically targeting macrophage and suggest that WA has the potential to be repurposed for clinically treating FH as an immunoregulator.
- |||||||||| Review, Journal: Autophagy, an accomplice or antagonist of drug resistance in HCC? (Pubmed Central) - Sep 16, 2021
This review focuses on autophagic proteins and explores the intricate relationship between autophagy and cancer stem cells, tumor-derived exosomes, and noncoding RNA. Clinical trials involved in autophagy inhibition combined with anticancer drugs are also concerned.
- |||||||||| Journal: Arsenite induces ferroptosis in the neuronal cells via activation of ferritinophagy. (Pubmed Central) - Sep 16, 2021
Co-treatment of arsenite with ferroptosis inhibitor ferrostatin-1, or autophagy inhibitors 3-MA and BafA1, all remarkably attenuated the cytotoxic effects of arsenite. These findings not only present a novel mechanism that arsenite triggers ferroptosis in the neuronal cells via activation of ferritinophagy, but also indicate that regulating ferritinophagy to control iron level may provide a clue for prevention against arsenite neurotoxicity.
- |||||||||| Journal: Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn's disease-associated adherent-invasive E. coli. (Pubmed Central) - Sep 15, 2021
Inhibition of these miRNAs in exosome-donor cells infected with AIEC LF82 abolished the increase in miR-30c and miR-130a levels in the released Exo-LF82 and in Exo-LF82-receiving cells, thus suppressing the inhibitory effect of Exo-LF82 on ATG5 and ATG16L1 expression and on autophagy-mediated AIEC clearance in Exo-LF82-receiving cells. Our study shows that upon AIEC infection, IECs secrete exosomes that can transfer specific miRNAs to recipient IECs, inhibiting autophagy-mediated clearance of intracellular AIEC.
- |||||||||| paracetamol / Generic mfg.
Journal: Autophagy impairment as a key feature for acetaminophen-induced ototoxicity. (Pubmed Central) - Sep 15, 2021 Inhibition of autophagy by knocking down of Atg5 and Atg7 aggravated APAP-induced ER and oxidative stress and increased apoptotic cell death. This study provides a better understanding of the mechanism responsible for APAP ototoxicity, which is important for future exploration of treatment strategies for the prevention of hearing loss caused by ototoxic medications.
- |||||||||| Tecentriq (atezolizumab) / Roche
Journal: Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma. (Pubmed Central) - Sep 15, 2021 Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Therapeutic targeting of DGKA-mediated macropinocytosis leads to phospholipid reprogramming in Tuberous Sclerosis Complex. (Pubmed Central) - Sep 15, 2021 To determine how the metabolic vulnerabilities of TSC2-deficient cells can be targeted, we performed a high-throughput screen utilizing the "Repurposing" library at the Broad Institute of MIT and Harvard (Cambridge, MA), with or without the autophagy inhibitor chloroquine...Collectively, these data indicate that DGKA supports macropinocytosis in TSC2-deficient cells to maintain phospholipid homeostasis and promote proliferation. Targeting macropinocytosis with ritanserin may represent a novel therapeutic approach for the treatment of TSC and LAM.
- |||||||||| Torin1 / InvivoGen
Journal: CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. (Pubmed Central) - Sep 15, 2021 This study aimed to screen the expression profiles of circRNA, miRNA, and mRNA of ovarian cancer cells induced by Torin 1 (10 µM)...In general, this study demonstrated that circRAB11FIP1 regulated ATG7 and ATG14 by sponging miR-129. The data suggested that circRAB11FIP1 might serve as a candidate biomarker for EOC diagnosis and treatment.
- |||||||||| Journal: MiR-127-3p targeting CISD1 regulates autophagy in hypoxic-ischemic cortex. (Pubmed Central) - Sep 15, 2021
Accordingly, the overexpression of CISD1 effectively inhibited the autophagic cell death and physiological dysfunction in the brain of HI injury, whereas si-CISD1 reversed the neuroprotective effects of KO-miR-127-3p. Our findings explained the underlying mechanism for HI injury, and miR-127-3p targeting CISD1 signal could be supposed as a new treatment strategy to prevent and treat HI injury.
- |||||||||| Juxtapid (lomitapide) / Amryt, Novelion
Journal: Targeting PP2A with lomitapide suppresses colorectal tumorigenesis through the activation of AMPK/Beclin1-mediated autophagy. (Pubmed Central) - Sep 14, 2021 More importantly, PP2A was identified as a direct target of lomitapide by limited proteolysis-mass spectrometry (LiP-SMap), and the bioactivity of lomitapide was attenuated in PP2A-deficient cells, suggesting that the anticancer effect of lomitapide occurs in a PP2A-dependent manner. Taken together, the results of the study reveal that lomitapide can be repositioned as a potential therapeutic drug for CRC treatment.
- |||||||||| Journal, IO biomarker: Cytotoxic Effects of Hellebrigenin and Arenobufagin Against Human Breast Cancer Cells. (Pubmed Central) - Sep 14, 2021
In addition, Helle-triggered G/M arrest was significantly corrected by wortmannin, suggesting autophagy induction contributed to Helle-induced cytotoxicity of breast cancer cells by modulating necrosis and cell cycle arrest. Collectively, our results suggested potential usefulness of both Helle and Areno in developing therapeutic strategies to treat patients with different types of breast cancer, especially ER-positive breast cancer.
- |||||||||| chloroquine phosphate / Generic mfg., dasatinib / Generic mfg.
Journal: Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43 in Glioblastoma Stem Cells. (Pubmed Central) - Sep 11, 2021 TAT-Cx43 exerts an antitumor effect both in nutrient-complete and nutrient-deprived environments, which constitutes an advantage over chloroquine and dasatinib, whose effects depend on nutrient environment. Finally, our analysis of the levels of autophagy-related proteins in healthy and glioma donors suggests that autophagy is upregulated in glioblastoma, further supporting the interest in inhibiting this process in the most aggressive brain tumor and the potential use of TAT-Cx43 as a therapy for this type of cancer.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: Autophagy positively regulates Wnt signaling in mice with diabetic retinopathy. (Pubmed Central) - Sep 11, 2021 In cultured Müller cells, rapamycin induced autophagy and activated Wnt signaling, while chloroquine, an autophagy inhibitor, inhibited autophagy and downregulated Wnt signaling, suggesting that autophagy could regulate Wnt signaling in mice retina and retinal cells. In summary, this study demonstrated that autophagy may positively regulate Wnt signaling in diabetic retinas, indicating a potential mechanism of Wnt signaling upregulation in DR and a possible novel therapeutic target of DR.
- |||||||||| Preclinical, Journal: EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus. (Pubmed Central) - Sep 11, 2021
From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p < 0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.
- |||||||||| Journal: RIP1/RIP3/MLKL Mediates Myocardial Function Through Necroptosis in Experimental Autoimmune Myocarditis. (Pubmed Central) - Sep 10, 2021
However, all necroptosis, apoptosis, and autophagy inhibitors independently reduce inflammatory infiltration in cardiomyocytes and improve cardiac conditions. Since apoptosis or autophagy is involved in many important cellular aspects, instead of suppressing these two major cell death processes, Nec1 can be developed as a potential therapeutic target for inflammatory myocarditis.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: Nitric Oxide Mediated Degradation of CYP2A6 via the Ubiquitin-Proteasome Pathway in Human Hepatoma Cells. (Pubmed Central) - Sep 10, 2021 This occurs via ubiquitination and proteasomal degradation, and does not require catalytic activity of the enzyme. This work adds to the growing knowledge of the selective effect and mechanism of action of NO on P450 enzymes, and suggests a possible novel mode of interaction between nicotine and NO in cigarette smokers.
- |||||||||| Journal: Defective lysosome reformation during autophagy causes skeletal muscle disease. (Pubmed Central) - Sep 10, 2021
Activation of TFEB-dependent de novo lysosome biogenesis did not compensate for loss of ALR in Inpp5k-/- muscle, revealing a dependence on this lysosome recycling pathway. Therefore, in muscle, ALR is indispensable for lysosome homeostasis during autophagy and when defective is associated with muscular dystrophy.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes. (Pubmed Central) - Sep 10, 2021 However, the levels of cholesterol and plasmalogens did not recover despite the restoration of peroxisome abundance following chloroquine treatment. Thus, PEX16 is indispensable for maintaining peroxisome homeostasis by regulating not only the commonly known biogenesis pathway but also the autophagic degradation of peroxisomes.
- |||||||||| Journal, IO biomarker: Effects of Osthole on Apoptosis and Autophagy of Human Tongue Cancer Tca8113 Cells (Pubmed Central) - Sep 9, 2021
Results Osthole significantly inhibited the proliferation and induced the apoptosis of Tca8113 cells in a concentration-dependent manner,and it reduced the cell colony formation.Western blot results showed that osthole could up-regulate the expression of Bax and cleaved caspase-3 and down-regulate that of Bcl-2.At the same time,it increased the expression of LC3Ⅱ and P62 and reduced that of LC3Ⅰ. Conclusion Osthole may inhibit the proliferation of Tca8113 cells by promoting cell apoptosis and blocking autophagy flow to inhibit autophagy.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Role of autophagy in midgut stem cells of silkworm Bombyx mori, during larval-pupal metamorphosis. (Pubmed Central) - Sep 9, 2021 For this purpose, two different doses of autophagy inhibitor chloroquine were administered to B. mori larvae on days 7 and 8 of the fifth larval stage...The obtained findings were evaluated in comparison with the control groups. Abnormalities in the formation of the pupal midgut after inhibition of autophagy showed the significance of the autophagy mechanism during this period.
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