- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: CDDO-Im ameliorates osteoarthritis and inhibits chondrocyte apoptosis in mice via enhancing Nrf2-dependent autophagy. (Pubmed Central) - Jul 8, 2022 Moreover, we confirmed that CDDO-Im (1-20 nM) dose-dependently activated Nrf2 pathway in TNF-α-treated chondrocytes, and its chondroprotective and autophagy-enhancing effects were significantly diminished when Nrf2 signaling was blocked by Nrf2 inhibitor ML385 (20 μM) or siRNA-mediated Nrf2 knockdown. Together, our results demonstrate that CDDO-Im exhibits prominent chondroprotective and anti-OA activities owing to its Nrf2 activation and autophagy-enhancing properties, which might provide new insights into the strategies of OA clinical prevention and treatment.
- |||||||||| Review, Journal: Autophagy is required for spermatogonial differentiation in the Drosophila testis. (Pubmed Central) - Jul 6, 2022
Furthermore, Bam deficiency leads to a failure in downstream mechanisms of the autophagic breakdown. These results suggest that the BMP-Bam signalling axis regulates developmental autophagy in the Drosophila testis, and that acidic breakdown of cellular materials is required for spermatogonial differentiation.
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Preclinical, Journal: Inhibition of autophagy with expression of NADPH oxidase subunit p22phox in preneoplastic lesions in a high-fat diet and streptozotocin-related hepatocarcinogenesis rat model. (Pubmed Central) - Jul 5, 2022 To study the effects of autophagy inducer carbamazepine (CBZ) in a high-fat diet (HFD)/streptozotocin (STZ)-related early hepatocarcinogenesis model, we determined autophagic flux by immunohistochemical analysis of autophagy marker expression in preneoplastic liver foci and compared that with the expression of the NADPH oxidase subunit...CBZ administration could induce autophagy and impair p22phox expression, as shown by altered expression of autophagy regulators (Atg5, Atg6, Lamp1, Lamp2, and Lc3), NADPH oxidase subunits (P22phox and P67phox), and antioxidant enzymes Gpx1 and Gpx2. These results suggest that inhibition of autophagy and induction of p22phox might contribute to HFD/STZ-related early hepatocarcinogenesis in rats; however, the effects of CBZ administration on the STZ/HFD-increased preneoplastic foci were marginal in this study.
- |||||||||| Journal: Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer's Disease. (Pubmed Central) - Jul 2, 2022
In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeutically.
- |||||||||| sevoflurane / Generic mfg.
Preclinical, Journal: FOXO3 Regulates Sevoflurane-Induced Neural Stem Cell Differentiation in Fetal Rats. (Pubmed Central) - Jul 1, 2022 Our results demonstrated that maternal exposure to 3.5% sevoflurane for 2 h during the mid-trimester induced NSC differentiation in the fetal brain through the activation of FOXO3. Autophagy inhibitor or lithium chloride reversed the improper differentiation of NSCs.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: The dual fates of exogenous tau seeds: lysosomal clearance vs. cytoplasmic amplification. (Pubmed Central) - Jun 30, 2022 The lysosome inhibitor bafilomycin inhibited vesicular clearance, whereas the proteasome inhibitor MG132 inhibited cytosolic clearance. Tau seeds that enter the cell thus have at least two fates: lysosomal clearance that degrades most tau, and entry into the cytosol, where seeds amplify, and are cleared by the proteasome.
- |||||||||| sirolimus / Generic mfg.
Journal: Impaired autophagy aggravates oxidative stress in mammary gland of dairy cows with clinical ketosis. (Pubmed Central) - Jun 29, 2022 For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagy-related protein abundance were measured...Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.
- |||||||||| chloroquine phosphate / Generic mfg.
A novel late-stage autophagy inhibitor that efficiently targets lysosomes and shows potent cytotoxic effect in lung cancer cells (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_1091; Cell viability after 24 h of known autophagy inhibitors (chloroquine and 3- Methyladenine) and LAI-1 treatments in three lung cancer cell lines with different genetic backgrounds, was evaluated by MTT assay...This effect results in a blockage of autophagy flux in the late-phase stage by inhibiting the fusion of autophagosomes and lysosomes and consequently, producing cell death at lower concentrations than other known autophagy inhibitors. Funding: Junta de Castilla y León and FEDER (BU067P20 grant).
- |||||||||| 5-fluorouracil / Generic mfg., chloroquine phosphate / Generic mfg., doxycycline / Generic mfg.
Decoding the molecular determinants that mediate autophagy in slow-cycling cancer cells. (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_1053; We analysed SCCCs survival in response to chloroquine and 5FU by flow cytometry...Finally, we detected a synergistic effect of the combination of a lysosomal inhibitor and 5FU in enhancing the death of SCCCs. Conclusion We propose DPPA3 as a new autophagy-specific component involved in the particular context of drug resistance and SCCCs, providing an innovative target autophagy-based therapeutic intervention for cancer relapse.
- |||||||||| 5-fluorouracil / Generic mfg., gemcitabine / Generic mfg.
Mechanical stress induces chemoresistance through ER stress/autophagy activation in pancreatic cancer cells (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_1031; A combined treatment employing chemotherapy with an autophagy inhibitor, and a mechanotherapeutic agent, showed promising results in increasing the overall-survival of pancreatic tumor-bearing mice. Conclusion Our results provide evidence that alleviation of intratumoral mechanical stresses with mechanotherapeutics combined with autophagy inhibitors can improve the efficacy of chemotherapeutic agents in pancreatic cancer.
- |||||||||| Zelboraf (vemurafenib) / Roche
New insights on melanoma treatment: how can seriniquinones benefit? (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_541; This work aims to elucidate the role of autophagy in the cytotoxicity of serinoquinones and the susceptibility of vemurafenib-resistant cells to these compounds...After treatments with bafilomycin A1 (autophagy inhibitor), rapamycin (autophagy inducer), Z-VAD-FMK (apoptosis inhibitor) or doxorubicin (apoptosis inducer), cells were submitted to MTT assay to determinate the respective IC 50 (half maximal inhibitory concentration) and to Western blotting analyses to evaluate key-protein expressions from autophagy and apoptosis pathways...Conclusion Due to its novel mechanism of action, seriniquinones have a great potential not only to inaugurate a new anticancer drug class but also to become a pharmacological tool to understand the role of dermcidin in the context of carcinogenesis and chemoresistance. This way, more studies are necessary and dermcidin silencing may bring new insights on this relationship.
- |||||||||| Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_361;
Conclusion Taken together, these data suggest that autophagy induced by Si306 and pro-Si306 has a protective role in GBM cells, and that autophagy modulation may be used to enhance the anticancer effects of SFKIs. In addition, as the ability of the SFKIs to induce autophagy was not diminished by the presence of the MDR phenotype makes these compounds promising for treatment of MDR cancers.
- |||||||||| temozolomide / Generic mfg.
Review, Journal: Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies. (Pubmed Central) - Jun 25, 2022 The current standard approach in GBM is surgery, followed by treatment with radiation and temozolomide (TMZ); however, GBM is highly resistant to current therapies, and the standard of care has not been revised over the last two decades, indicating an unmet need for new therapies...We also discuss novel therapeutic strategies, including molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs, from basic research findings to ongoing clinical trials. Although the development of effective therapies for GBM is still challenging, this review provides a better understanding of GSCs and offers future directions for successful GBM therapy.
- |||||||||| Review, Journal: Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management. (Pubmed Central) - Jun 25, 2022
Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.
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