- |||||||||| temozolomide / Generic mfg.
Biomarker, Journal, Heterogeneity, PARP Biomarker: A heat shock protein 90 inhibitor reduces oncoprotein expression and induces cell death in heterogeneous glioblastoma cells with EGFR, PDGFRA, CDK4, and NF1 aberrations. (Pubmed Central) - Jan 11, 2022
This study expands our knowledge of the pharmacological effects of sesamin on T-cell lymphoma, and provides a theoretical basis for the development of new antitumour drugs and treatments for T-cell lymphoma. Taken together, AUY922 led to GBM cell death via apoptosis and autophagy, and reduced the mRNA and protein expression of EGFR, PDGFRA, CDK4, and NF1in heterogeneous GBM cells.
- |||||||||| Journal: The exploitation of host autophagy and ubiquitin machinery by Mycobacterium tuberculosis in shaping immune responses and host defense during infection. (Pubmed Central) - Jan 11, 2022
The role of Ub-binding receptors and their mode of autophagy regulation is also explained. We also discuss the co-opting and utilization of the host Ub system by M. tb for its survival and virulence.Abbreviations: APC: anaphase promoting complex/cyclosome; ATG5: autophagy related 5; BCG: bacille Calmette-Guerin; C2: Ca-binding motif; CALCOCO2: calcium binding and coiled-coil domain 2; CUE: coupling of ubiquitin conjugation to ER degradation domains; DUB: deubiquitinating enzyme; GABARAP: GABA type A receptor-associated protein; HECT: homologous to the E6-AP carboxyl terminus; IBR: in-between-ring fingers; IFN: interferon; IL1B: interleukin 1 beta; KEAP1: kelch like ECH associated protein 1; LAMP1: lysosomal associated membrane protein 1; LGALS: galectin; LIR: LC3-interacting region; MAPK11/p38: mitogen-activated protein kinase 11; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAPK8/JNK: mitogen-activated protein kinase 8; MHC-II: major histocompatibility complex-II; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; NFKB1/p50: nuclear factor kappa B subunit 1; OPTN: optineurin; PB1: phox and bem 1; PE/PPE: proline-glutamic acid/proline-proline-glutamic acid; PknG: serine/threonine-protein kinase PknG; PRKN: parkin RBR E3 ubiquitin protein ligase; RBR: RING-in between RING; RING: really interesting new gene; RNF166: RING finger protein 166; ROS: reactive oxygen species; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TNF: tumor necrosis factor; TRAF6: TNF receptor associated factor 6; Ub: ubiquitin; UBA: ubiquitin-associated; UBAN: ubiquitin-binding domain in ABIN proteins and NEMO; UBD: ubiquitin-binding domain; UBL: ubiquitin-like; ULK1: unc-51 like autophagy activating kinase 1.
- |||||||||| Clinical, Journal: Gutting it Out: Developing Effective Immunotherapies for Patients With Colorectal Cancer. (Pubmed Central) - Jan 8, 2022
The search for therapies that can be combined with current approaches to increase their efficacy, and new knowledge of the biology of CRC are pivotal to improve the care of patients suffering from this disease. Here, we review the basic immunobiology of CRC, current "state-of-the-art" immunotherapies and define those areas with greatest therapeutic promise for the future.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Journal: Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells. (Pubmed Central) - Jan 8, 2022
Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3β and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3β signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.
- |||||||||| gefitinib / Generic mfg.
Journal: Inhibition of autophagy by YC-1 promotes gefitinib induced apoptosis by targeting FOXO1 in gefitinib-resistant NSCLC cells. (Pubmed Central) - Jan 8, 2022
Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC1a protein degradation. (Pubmed Central) - Jan 8, 2022
Moreover, lysosome inhibitor chloroquine (CQ) and autophagy inhibitor 3-methyladeniine (3-MA) could reverse the reduction of ASIC1a protein caused by estrogen, indicating that autophagy-lysosome pathway contributes to estrogen-induced degradation of ASIC1a protein...Additionally, adenosine 5'-monophosphate (AMP)-activated protein kinase/unc-51-like kinase 1 (AMPK-ULK1) signaling pathway was activated by estrogen treatment, which was abrogated by Esrra-silencing, and AMPK-specific inhibitor Compound C pretreatment could reduce estrogen-induced downregulation of ASIC1a protein. Taken together, these results indicate that estrogen could promote autophagy-lysosome pathway-dependent ASIC1a protein degradation and protect against acidosis-induced cytotoxicity, the mechanisms of which might relate to Esrra-AMPK-ULK1 signaling pathway.
- |||||||||| dorsomorphin (Compound C) / EMD Serono
Journal: Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells. (Pubmed Central) - Jan 8, 2022
Accordingly, exposure to dorsomorphin (Compound C), an AMPK inhibitor, and AICAR, an AMPK activator, respectively inhibited and stimulated BA-induced autophagy in EJ and T24 cells. The effects of Bmi-1 overexpression in vitro and decreased Bmi-1 expression in BA-treated T24 cell xenografts in nude mice suggested that downregulation of Bmi-1 is the underlying mechanism in BA-mediated, autophagy-dependent apoptosis.
- |||||||||| ganetespib (ADX-1612) / Aldeyra, MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: Hsp90/C terminal Hsc70-interacting protein regulates the stability of Ikaros in acute myeloid leukemia cells. (Pubmed Central) - Jan 7, 2022
In addition, the knockdown of Ikaros effectively inhibits the proliferation of leukemia cells, but this phenomenon could be rescued by Ikaros overexpression. Collectively, our findings indicate that the interplay between HSP90 and CHIP regulates the stability of Ikaros in AML cells, which provides a novel strategy for AML treatment through targeting the HSP90/Ikaros/CHIP axis.
- |||||||||| Journal: Emerging role of autophagy in anti-tumor immunity: Implications for the modulation of immunotherapy resistance. (Pubmed Central) - Jan 7, 2022
A number of studies have demonstrated that optimal induction or inhibition of autophagy may lead to effective therapeutic regimens when combined with immunotherapy. This review discusses the important roles of autophagy in tumor cells, immune cells and stromal cells in the context of tumor immunity, and the potential of combining the autophagy-based therapy with immunotherapy as novel therapeutic approaches against cancer.
- |||||||||| metformin / Generic mfg.
Journal: Involvement of autophagy in diosgenin‑induced megakaryocyte differentiation in human erythroleukemia cells. (Pubmed Central) - Jan 7, 2022
Autophagy was modulated before or after the induction of megakaryocyte differentiation using 3‑methyladenine (3‑MA, autophagy inhibitor) and metformin (Met, autophagy initiation activator)...On the other hand, autophagy activation increased GpV genomic expression, but did not change the nuclear maturation profile after HEL cells treatment with Met. It was concluded that autophagy inhibition had a more prominent effect on the diosgenin‑differentiated cells than autophagy activation.
- |||||||||| Journal: SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response. (Pubmed Central) - Jan 7, 2022
Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19.
- |||||||||| AZD8055 / AstraZeneca, capivasertib (AZD5363) / Otsuka, AstraZeneca
Journal: Resolvin D1 attenuates CCl4 Induced Liver Fibrosis by Inhibiting Autophagy-Mediated HSC activation via AKT/mTOR Pathway. (Pubmed Central) - Jan 7, 2022
In addition, using AZD5363 (an AKT inhibitor that activates autophagy) and AZD8055 (an mTOR inhibitor, another autophagy activator), we further verified that RvD1 suppressed autophagy-mediated HSC activation and alleviated CCl4 induced liver fibrosis partly through AKT/mTOR pathway. Overall, these results demonstrate that RvD1 treatment is expected to become a novel therapeutic strategy against liver fibrosis.
- |||||||||| Journal: Co-Targeting Plk1 and DNMT3a in Advanced Prostate Cancer. (Pubmed Central) - Jan 6, 2022
Mechanistically, it is shown that Plk1 phosphorylation of DNMT3a leads to its degradation in mitosis and that DNMT3a represses Plk1 transcription to inhibit autophagy in interphase, suggesting a negative feedback loop between these two proteins. Finally, a combination of the DNMT inhibitor 5-Aza-2'-deoxycytidine (5-Aza) with inhibition of Plk1 suppresses PCa synergistically.
- |||||||||| clozapine / Generic mfg.
Journal: Stimulating TRPM7 suppresses cancer cell proliferation and metastasis by inhibiting autophagy. (Pubmed Central) - Jan 5, 2022
Here, we show that the activation of TRPM7 channel stimulated by chemical agonists of TRPM7, Clozapine or Naltriben, inhibited autophagy via mediating Zn release to the cytosol, presumably from the intracellular Zn-accumulating vesicles where TRPM7 localizes...Functionally, we demonstrate that the autophagy inhibition mediated by TRPM7 triggered cell death and suppressed metastasis of cancer cells in vitro, more importantly, restricted tumor growth and metastasis in vivo, by evoking apoptosis, cell cycle arrest, and reactive oxygen species (ROS) elevation. These findings represent a strategy for stimulating TRPM7 to combat cancer.
- |||||||||| SP600125 / BMS
Journal, IO biomarker: DUSP4 inhibits autophagic cell death in PTC by inhibiting JNK-BCL2-Beclin1 signaling. (Pubmed Central) - Jan 4, 2022
In addition, we further identified the significance of the JNK-BCL2-Beclin1-autophagy signaling pathway on DUSP4-regulated PTC carcinogenesis by combining knockdown of DUSP4 with a JNK-specific inhibitor (SP600125)...We further extended the in vitro experiments by injecting K1 cells transduced with DUSP4-silencing vector subcutaneously into nude mice. In vivo assays showed that DUSP4 silencing not only inhibited tumor growth, but also promoted JNK and BCL2 phosphorylation and LC3II expression.Overall, DUSP4 inhibits BCL2-Beclin1- autophagy signaling through negatively regulating JNK activity, thus inhibiting PTC oncogenesis.This study provides more potential clues for the prevention and cure of PTC.
- |||||||||| sirolimus / Generic mfg.
Journal, IO biomarker: Characterization of the effects of heat stress on autophagy induction in the pig oocyte. (Pubmed Central) - Jan 4, 2022
Our results here suggest that HS increases autophagy induction in the oocyte during IVM, and that artificial induction of autophagy increases the maturation rate of oocytes during IVM. These data support autophagy as a potential mechanism activated in the oocyte during HS to recycle damaged cellular components and maintain developmental competence.
- |||||||||| Journal: Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy. (Pubmed Central) - Jan 4, 2022
Interestingly, our results indicated that TRPM2 deficiency could further activate AMPK rather than Beclin1 activity, suggesting that TRPM2 inhibits autophagy by regulating the AMPK/mTOR pathway in I-R. In conclusion, our study reveals that ROS-activated TRPM2 inhibits autophagy by downregulating the AMPK/mTOR pathway, which results in neuronal death induced by cerebral I-R, further supporting that TRPM2 might be a potential drug target for cerebral ischemic injury therapy.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Knockdown of lncRNA HIF1A-AS2 increases drug sensitivity of SCLC cells in association with autophagy. (Pubmed Central) - Jan 4, 2022
The expression of HIF1A-AS2 was silenced by siRNA in doxorubicin-sensitive H69 and doxorubicin-resistant H69AR cells...Knockdown of HIF1A-AS2 increased drug sensitivity of SCLC cells in relation to autophagy. Therefore, hypoxia-HIF1A-AS2-autophagy interaction is thought to be determinative in drug sensitivity of these cells.
- |||||||||| Amphinex (fimaporfin) / PCI Biotech
Clinical, Journal: Inhibiting autophagy increases the efficacy of low-dose photodynamic therapy. (Pubmed Central) - Jan 4, 2022
Here, we show that photochemical treatment with the PCI-photosensitizer TPCS/fimaporfin results in both induction of autophagy and inhibition of the autophagic flux...An active autophagic response and the presence of p62, however, is important for cancer cells to survive low-dose TPCS-PDT. Thus, targeting both p62 and autophagy together and independently, in a light-controlled/PCI based delivery of cancer therapeutics could increase the effectiveness of the treatment regime.
- |||||||||| Journal: DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer. (Pubmed Central) - Jan 4, 2022
In xenograft mouse model, our results also showed that DHOK activates the mTOR signaling pathway, decreases autophagy level and inhibits the tumorigenesis of colon cancer. Taken together, we revealed the molecular mechanism of DHOK against cancer and our results also demonstrate great potential of DHOK in the treatment of colorectal cancer.
- |||||||||| Journal: TNFAIP8L2/TIPE2 impairs autolysosome reformation via modulating the RAC1-MTORC1 axis. (Pubmed Central) - Jan 1, 2022
Furthermore, TNFAIP8L2 deficiency can exacerbate the inflammatory response and lung injury by controlling the MTOR activity in an LPS-induced mouse endotoxemia model. Our study reveals a novel role of TNFAIP8L2 in autophagy by regulating the RAC1-MTORC1 axis that supports its potential as a target for therapeutic treatment.Abbreviations: ALR: autophagic lysosome reformation; BafA: bafilomycin A; BMDMs: bone marrow-derived macrophages; Co-IP: Co-Immunoprecipitation; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTORC1: mechanistic target of rapamycin kinase complex 1; RAPA: rapamycin; RPS6: ribosomal protein S6; SQSTM1/p62: sequestosome 1; Starv: Starvation; TNFAIP8L2/TIPE2: tumor necrosis factor-alpha-induced protein-8 like-2.
- |||||||||| Journal: TMEM100 induces cell death in non‑small cell lung cancer via the activation of autophagy and apoptosis. (Pubmed Central) - Jan 1, 2022
Mechanistically, TMEM100 was demonstrated to induce autophagy in A549 cells via inhibiting the PI3K/AKT signaling pathway, whereas inhibiting autophagy using bafilomycin A1 significantly enhanced TMEM100‑induced apoptosis to compensate for the cell death. In conclusion, these findings suggested that TMEM100 may serve as a tumor suppressor in NSCLC and promote autophagy via inhibiting the PI3K/AKT signaling pathway.
- |||||||||| Journal: Computational design of binder as the LC3-p62 protein-protein interaction. (Pubmed Central) - Jan 1, 2022
In this article, the computation method was used to identify the hot spot and design peptides as the binder of LC3-p62 PPI. Findings from this work provide a reference for the follow-up research of discovering small molecule inhibitors targeting LC3-p62 PPI.
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