- |||||||||| chloroquine phosphate / Generic mfg., estradiol valerate / Generic mfg., sirolimus / Generic mfg.
Journal: Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway. (Pubmed Central) - Aug 7, 2022
In this study, knockdown of circ_CCNB2 was shown to promote PCa radiosensitivity through autophagy repression by miR-30b-5p/KIF18A axis, developing a molecular resistance mechanism of PCa radiotherapy and a feasible strategy to increase radiosensitivity. Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway.
- |||||||||| Journal: GJA1 reverses arsenic-induced EMT via modulating MAPK/ERK signaling pathway. (Pubmed Central) - Aug 6, 2022
These results suggested that GJA1 restrained the carcinogenic effect of sodium arsenite by limiting MAPK/ERK signaling, and GJA1 expression was decreased by arsenic-activated autophagy. In addition, interventions directed at enhancing the level or functional activity of GJA1 could be of preventive and therapeutic interest.
- |||||||||| Journal: The cross-talk of autophagy and apoptosis in breast carcinoma: implications for novel therapies? (Pubmed Central) - Aug 6, 2022
Hence, combination of antiautophagic agents with the enhancement of apoptosis may restore apoptosis and provide a therapeutic advantage against breast cancer. In this review, we discuss the cross-talk of autophagy and apoptosis and the diverse facets of autophagy in breast cancer cells leading to novel models for more effective therapeutic strategies.
- |||||||||| sirolimus / Generic mfg.
Journal: A Highly Selective GSK-3β Inhibitor CHIR99021 Promotes Osteogenesis by Activating Canonical and Autophagy-Mediated Wnt Signaling. (Pubmed Central) - Aug 6, 2022
Autophagy inhibitor 3MA partially reduces C91-induced osteoblast differentiation and mineralization; autophagy inducer Rapamycin increases the expression of β-catenin to promote osteogenic differentiation, but cannot alleviate the inhibition of Triptonide on C91-induced osteogenic differentiation, indicating the crosstalk of canonical Wnt signaling and autophagy regulates C91-induced osteoblast differentiation...During this period, the C91 is released by 83.0% and the cell viability maintained at 96.4%. Therefore, the small molecule Wnt agonist C91 promotes osteogenesis through caonical and autophagy-mediated Wnt signaling pathway with an option for translational application.
- |||||||||| chloroquine phosphate / Generic mfg., dactinomycin / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers. (Pubmed Central) - Aug 5, 2022
We also validate that SH3BGRL expression is positively correlated with that of PIK3C3 or ATG12, as well as the constitutive occurrence of autophagy in clinical breast cancer tissues. Taken together, our data reveal that SH3BGRL upregulation would be a key driver to the acquired chemotherapy resistance through autophagy enhancement in breast cancer while targeting SH3BGRL could be a potential therapeutic strategy against breast cancer.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Autophagy inhibition mediated by MCOLN1/TRPML1 suppresses cancer metastasis via regulating a ROS-driven TP53/p53 pathway. (Pubmed Central) - Aug 5, 2022
In summary, our findings have established a mechanism by which autophagy inhibition suppresses metastasis via the ROS-TP53 signaling pathway. More importantly, our study demonstrates that autophagy inhibition through stimulation of MCOLN1 could evidently be one of the therapeutic potentials for combating cancer metastasis.Abbreviations: 3-MA: 3-methyladenine; AA: amino acid; ATG5: autophagy related 5; ATG12: autophagy related 12; Baf-A1: bafilomycin A; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CQ: chloroquine; DMEM: Dulbecco's Modified Eagle Medium; EMT: epithelial-mesenchymal transition; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HEK: human embryonic kidney; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MMP: matrix metallopeptidase; NC: negative control; NRK: normal rat kidney; PBS: phosphate-buffered saline; shRNA: short hairpin RNA; siRNA: short interfering RNA; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Autophagy modulates cell fate decisions during lineage commitment. (Pubmed Central) - Aug 5, 2022
Thus, our results indicate that autophagy-mediated SOX2 turnover is a determining factor for lineage commitment. These findings will deepen our understanding of development and lead to improved methods to derive different lineages and cell types.Abbreviations: ACTB: Actin, beta; ATG: Autophagy-related; BafA1: Bafilomycin A; CAS9: CRISPR associated protein 9; CQ: Chloroquine; DE: Definitive endoderm; hESCs: Human Embryonic Stem Cells; hiPSCs: Human Induced Pluripotent Stem Cells; LAMP1: Lysosomal Associated Membrane Protein 1; MAP1LC3: Microtubule-Associated Protein 1 Light Chain 3; MTOR: Mechanistic Target Of Rapamycin Kinase; NANOG: Nanog Homeobox; PAX6: Paired Box 6; PE: Phosphatidylethanolamine; POU5F1: POU class 5 Homeobox 1; PRKAA2: Protein Kinase AMP-Activated Catalytic Subunit Alpha 2; SOX2: SRY-box Transcription Factor 2; SQSTM1: Sequestosome 1; ULK1: unc-51 like Autophagy Activating Kinase 1; WDFY3: WD Repeat and FYVE Domain Containing 3.
- |||||||||| chloroquine phosphate / Generic mfg., sirolimus / Generic mfg.
Journal: 2AB protein of Senecavirus A antagonizes selective autophagy and type I interferon production by degrading LC3 and MARCHF8. (Pubmed Central) - Aug 5, 2022
During the autophagy process, the SVA 2AB protein targeted MARCHF8 and MAVS forming a large complex for degradation to deactivate IFN-I signaling. Together, our study reveals the molecular mechanisms of selective autophagy in the host against viruses and reveals potential viral strategies to evade the autophagic process and IFN-I signaling for successful pathogenesis.Abbreviations: Baf A: bafilomycin A; Co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; hpi: hours post-infection; IFN: interferon; ISG: IFN-stimulated gene; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF8/MARCH8: membrane associated ring-CH-type finger 8; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; Rapa: rapamycin; RT: room temperature; siRNA: small interfering RNA; SVA: Senecavirus A; TCID: 50% tissue culture infectious doses.
- |||||||||| chloroquine phosphate / Generic mfg., sirolimus / Generic mfg.
Journal: Autophagy regulates differentiation of ovarian granulosa cells through degradation of WT1. (Pubmed Central) - Aug 5, 2022
Finally, decreased expression of several autophagy-related genes, as well as reduced LC3-II:LC3-I and elevated SQSTM1/p62 protein levels, which are indications of decreased autophagy, were detected in GCs from biochemical premature ovarian insufficiency patients. In summary, our study reveals that autophagy regulates the differentiation of ovarian GCs by degrading WT1 and that insufficient autophagy might be involved in ovarian dysfunction.
- |||||||||| Journal: Follicular lymphoma-associated mutations in the V-ATPase chaperone VMA21 activate autophagy creating a targetable dependency. (Pubmed Central) - Aug 5, 2022
Of translational significance, the compensatory activation of autophagy creates a dependency for survival for VMA21-mutated primary human FL as shown using inhibitors to ULK1, the proximal autophagy-regulating kinase. Using high-throughput microscopy-based screening assays for autophagy-inhibiting compounds, we identify multiple clinical grade cyclin-dependent kinase inhibitors as promising drugs and thus provide new rationale for innovative clinical trials in FL harboring aberrant V-ATPase.
- |||||||||| Review, Journal: Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents. (Pubmed Central) - Aug 4, 2022
A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.
- |||||||||| chloroquine phosphate / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Effect of Chloroquine on Doxorubicin-induced Apoptosis in A549 Cells. (Pubmed Central) - Aug 4, 2022
Chloroquine enhances doxorubicin-induced and oxidative stress-mediated apoptosis. This mechanism may involve the dephosphorylation of extracellular-signal-regulated kinases.
- |||||||||| sirolimus / Generic mfg.
Journal: Biliary Drainage Reduces Intestinal Barrier Damage in Obstructive Jaundice by Regulating Autophagy. (Pubmed Central) - Aug 3, 2022
The rats were separated into two groups that received the autophagy activator rapamycin (RAPA) or the autophagy inhibitor 3-methyladenine (3-MA) to further investigate whether biliary drainage could alleviate the inflammatory response, oxidative stress, mitochondrial complex IV damage, and thus barrier damage in rats with OJ...When OJ rats were treated with 3-MA, intestinal mucosal injury, intestinal mitochondrial injury, and oxidative stress were all aggravated (P < 0.05). Biliary drainage can reduce the expression of inflammatory factors, oxidative stress, and mitochondrial injury by inducing intestinal mucosal autophagy in OJ rats, thus suggesting its role in the alleviation of intestinal mucosal injury.
- |||||||||| Review, Journal: Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance. (Pubmed Central) - Aug 2, 2022
Also, we focused on the current understanding of the role of the EMT and TME, including its relation to gut microbiota and immune cells, in autophagic manipulation of CRC. We believe that there is a potential link between autophagy, TME, EMT, and drug resistance, suggesting that further studies are needed to explore this aspect.
- |||||||||| Journal: Re-evaluation of the role of autophagy in thyroid cancer treatment. (Pubmed Central) - Jul 31, 2022
Thus, the present findings relating to several anticancer therapeutics and three thyroid cancer cell lines demonstrate the pro-survival effect of autophagy in thyroid cancer treatment. Although the present study only involved cell lines, it provides evidence for the beneficial combination of the anticancer therapeutic modalities with autophagy inhibitors, and proposes that autophagy inhibitors may serve as a possible adjunctive therapy for thyroid cancer.
- |||||||||| Journal: Gga-miR-30c-5p Suppresses Avian Reovirus (ARV) Replication by Inhibition of ARV-Induced Autophagy via Targeting ATG5. (Pubmed Central) - Jul 31, 2022
Importantly, gga-miR-30c-5p suppressed ARV replication by inhibition of ARV-induced autophagy via targeting autophagy related 5 (ATG5) accompanied by suppression of virus-induced syncytium formation, thus serving as an important antivirus factor in host response against ARV infection. These findings will further our understanding of how host cells combat against ARV infection by self-encoded small RNAs and may be used as a potential target for intervening ARV infection.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal, PD(L)-1 Biomarker, IO biomarker: Autophagy blockade potentiates cancer-associated immunosuppression through programmed death ligand-1 upregulation in bladder cancer. (Pubmed Central) - Jul 30, 2022
The autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (Baf-A1) increased PD-L1 expression in BC cells through the ERK-JNK-c-Jun signal-transduction pathway...Our results provide evidence that autophagy blockade and its regulatory pathway affect cancer-associated immunosuppression through PD-L1 elevation. Thus, the coadministration of autophagy inhibitors and a PD-L1 immune checkpoint blockade provides a potential therapeutic approach for treating BC.
- |||||||||| pramipexole IR / Generic mfg.
Preclinical, Journal: Pramipexole inhibits astrocytic NLRP3 inflammasome activation via Drd3-dependent autophagy in a mouse model of Parkinson's disease. (Pubmed Central) - Jul 30, 2022
Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 μM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: High glucose induces an early and transient cytoprotective autophagy in retinal Müller cells. (Pubmed Central) - Jul 30, 2022
Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy. A short-term HG challenge triggers in rMC-1 cells a process improving the ability to cope with stressful conditions, which involves ERK and an early and transient autophagy activation.
- |||||||||| acetylcysteine solution / Generic mfg.
Journal: Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells. (Pubmed Central) - Jul 29, 2022
ROS scavenger N-acetylcysteine (NAC) decreased PHA-elevated autophagy activity, implying that PHA-induced ROS may be required for autophagy induction in breast cancer cells...In contrast, NAC and apoptosis inhibitor Z-VAD-FMK blocked the proportion of annexin V/7-aminoactinmycin D and the activation of caspases. Taken together, PHA induced ROS to promote autophagy, which might play an antioxidant and anti-apoptotic role in breast cancer cells.
- |||||||||| chloroquine phosphate / Generic mfg., cisplatin / Generic mfg.
Journal: A Novel Late-Stage Autophagy Inhibitor That Efficiently Targets Lysosomes Inducing Potent Cytotoxic and Sensitizing Effects in Lung Cancer. (Pubmed Central) - Jul 29, 2022
Finally, LAI-1 sensitized cancer cells to the first-line chemotherapeutic agent cisplatin. Altogether, LAI-1 is a new late-stage autophagy inhibitor that causes lysosomal dysfunction and the blockage of autophagolysosome formation, as well as potently induces cancer cell death and sensitization to conventional treatments at lower concentrations than other known autophagy inhibitors, appearing as a potential new therapeutic approach to overcome cancer resistance.
- |||||||||| Review, Journal: Autophagy: A Key Player in Pancreatic Cancer Progression and a Potential Drug Target. (Pubmed Central) - Jul 29, 2022
This review will outline the autophagy pathway and its regulation, in addition to the genetic landscape and tumor microenvironment that contribute to pancreatic cancer severity. Moreover, this review will also discuss the mechanisms of novel therapeutic strategies that inhibit autophagy and how they could be used to suppress tumor progression.
- |||||||||| hydroxychloroquine / Generic mfg.
Journal: Chrysin Induces Apoptosis and Autophagy in Human Melanoma Cells via the mTOR/S6K Pathway. (Pubmed Central) - Jul 29, 2022
In A375SM, the early autophagy inhibitor 3-methyladenine (3-MA) was unaffected; however, cell viability decreased when treated with the late autophagy inhibitor hydroxychloroquine (HCQ)...Chrysin also decreased the phosphorylation of mTOR/S6K pathway proteins, indicating that this pathway is involved in chrysin-induced apoptosis and autophagy for A375SM and A375P. However, studies to elucidate the mechanisms of autophagy and the action of chrysin in vivo are still needed.
- |||||||||| Review, Journal: Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy. (Pubmed Central) - Jul 29, 2022
In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.
- |||||||||| Journal: Effect of Autophagy Inhibitors on Radiosensitivity in DNA Repair-Proficient and -Deficient Glioma Cells. (Pubmed Central) - Jul 29, 2022
The extent of the DNA damage response remained high in the DNA-PKcs deficient cells following exposure to radiation, indicating their inability to repair the newly formed DNA-DSBs. On the other hand, radioresistant M059K cells showed more DNA damage response only when autophagy inhibitors were used with radiation, suggesting that the combination of autophagy inhibitors with radiation may interfere with DNA repair efficiency.
- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo. (Pubmed Central) - Jul 29, 2022
In the presence of chloroquine, an autophagy inhibitor, we observed an increased mortality of cells, implying a cytoprotective role of autophagy...The results presented in this study display a strong effect of compound CarbZDChin on malignant cell growth. Having in mind the important role of inflammation in cancer development, these results have a significant impact and are worthy of further evaluation.
- |||||||||| acetylcysteine solution / Generic mfg.
Preclinical, Journal, PARP Biomarker, IO biomarker: T-2 Toxin Induces Apoptotic Cell Death and Protective Autophagy in Mouse Microglia BV2 Cells. (Pubmed Central) - Jul 29, 2022
N-acetylcysteine (NAC) supplementation significantly attenuated T-2 toxin-induced cytotoxicity...Taken together, our results reveal that T-2 toxin-induced cytotoxicity in BV2 cells involves the production of ROS, the activation of the mitochondrial apoptotic pathway, and the inhibition of the Nrf2/HO-1 pathway. Our study offers new insight into the underlying molecular mechanisms in T-2 toxin-mediated neurotoxicity.
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