- |||||||||| hydroxychloroquine / Generic mfg.
Journal: ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction. (Pubmed Central) - Mar 15, 2022 The elevated levels of propionate in Acss3 mice similarly drive adipocyte autophagy, and pharmacological inhibition of autophagy using hydroxychloroquine ameliorates obesity, hepatic steatosis and insulin resistance of the Acss3 mice. These results establish ACSS3 as the key enzyme for propionate metabolism and demonstrate that accumulation of propionate promotes obesity and Type 2 diabetes through triggering adipocyte autophagy.
- |||||||||| Review, Journal: Pharmacological basis and new insights of deguelin concerning its anticancer effects. (Pubmed Central) - Mar 12, 2022
Deguelin inhibits tumor cell propagation and malignant transformation through targeting angiogenesis, targeting lymphangiogenesis, targeting focal adhesion kinase (FAK), inhibiting the CtsZ/FAK signaling pathway, targeting epithelial-mesenchymal transition (EMT), the NF-κB signaling pathway, regulating NIMA-related kinase 2 (NEK2). In addition, deguelin possesses other biological activities, such as targeting cell cycle arrest, modulation of autophagy, inhibition of hedgehog pathway, inducing differentiation of mutated NPM1 acute myeloid leukemia etc. Therefore, deguelin is a promising chemopreventive agent for cancer therapy.
- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: The Role of Autophagy in Murine Cytomegalovirus Hepatitis. (Pubmed Central) - Mar 11, 2022 Compared with the untreated infected group, increased transcription level of MCMV glycoprotein B (gB), increased expression levels of interleukin1-β (IL-1β), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), decreased expression level of type I interferon α (IFN-α), as well as aggravated liver pathological injury were detected in starvation-treated infected group on days 3 and 7 p.i.; whereas decreased transcription level of MCMV gB, decreased expression levels of IL-1β, AST and ALT, increased expression level of type I IFN-α, as well as alleviated liver pathological injury were detected in chloroquine (CQ)-treated infected group on day 3 p.i. In conclusion, autophagy is inhibited through activating the PI3K/Akt/mTOR pathway in the liver of BALB/c mice during MCMV infection, and autophagy may promote MCMV replication and aggravate liver pathological damage and inflammation. Further understanding of the interactions between autophagy and MCMV infection and its potential mechanism may bring new important cues to the control of MCMV infection and antiviral therapy.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Luteolin Induces Apoptosis and Autophagy in HCT116 Colon Cancer Cells via p53-Dependent Pathway. (Pubmed Central) - Mar 11, 2022 We identified that luteolin can induce autophagy in p53 wild-type cells but not in p53 mutant cells, suggesting that luteolin-induced autophagy is p53-dependent; however, chloroquine-mediated inhibition of autophagy did not alter cytotoxicity and apoptosis of cells treated with luteolin. In conclusion, the present data showed that luteolin inhibits the growth of HCT116 colon cancer cells through p53-dependent regulation of apoptosis and cell cycle arrest regardless of the induction of autophagy.
- |||||||||| bortezomib / Generic mfg.
Journal: Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1. (Pubmed Central) - Mar 11, 2022 USP12 depletion, concomitant with a reduced expression of HMGB1, suppressed autophagy and increased the sensitivity of resistant cells to BTZ. Collectively, our findings have identified an important role of the deubiquitylase USP12 in pro-survival autophagy and resultant BTZ resistance in MM by stabilizing HMGB1, suggesting that the USP12/HMGB1 axis might be pursued as a potential diagnostic and therapeutic target in human MM.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis. (Pubmed Central) - Mar 11, 2022 In contrast, the inhibitors of endosomal acidification bafilomycin A1 and chloroquine increased levels of LC3-II, due to reduced degradation in acidic lysosomes...Finally, EACC, which inhibits the fusion of autophagosomes with lysosomes, promoted LC3 degradation possibly by the proteasome. Targeting LAP with small molecule inhibitors is important given its emerging role in infectious and autoimmune diseases.
- |||||||||| Journal: Aquaporin-9 facilitates liver regeneration following hepatectomy. (Pubmed Central) - Mar 11, 2022
Adeno-associated virus (AAV)-mediated expression of hepatic expression of aquaglyceroporins AQP9 and AQP3 in AQP9 mice, but not water-selective channel AQP4, fully rescued the impaired liver regeneration phenotype as well as the oxidative injury and abnormal glucose metabolism. Our data revealed a pivotal role of AQP9 in liver regeneration by regulating hepatocyte HO homeostasis and glucose metabolism, suggesting AQP9 as a novel target to enhance liver regeneration following injury, surgical resection or transplantation.
- |||||||||| Journal: TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation. (Pubmed Central) - Mar 11, 2022
Tripartite motif-containing 14 (TRIM14) deficiency in dendritic cells significantly impaired the expression of the KDM4D-directed proinflammatory cytokines interleukin 12 (Il12) and Il23 and protected mice from autoimmune inflammation. Taken together, these findings highlight the cross-talk between epigenetic regulation and autophagy and suggest TRIM14 is a potential target of therapeutic intervention for inflammation-related diseases.
- |||||||||| Journal: Autophagy induction regulates aquaporin 3-mediated skin fibroblasts aging. (Pubmed Central) - Mar 9, 2022
A novel ARlncRNA signature for LUAD prognostic prediction was constructed, which had better efficacy than the TNM stage and used to propose potential therapeutic regimens for LUAD patients. Thus, our study indicates that AQP3 controls skin fibroblasts photoaging by regulating autophagy and represents a potential target for future interventions against skin aging.
- |||||||||| Preclinical, Journal: Autophagy modulation alleviates cryoinjury in murine spermatogonial stem cell cryopreservation. (Pubmed Central) - Mar 9, 2022
Thus, our study indicates that AQP3 controls skin fibroblasts photoaging by regulating autophagy and represents a potential target for future interventions against skin aging. A basal level of autophagy plays a critical role in the pro-survival response of frozen SSCs after thawing; herein, a new approach by which SSC cryoprotective efficiency can be improved was identified.
- |||||||||| sirolimus / Generic mfg.
Journal: IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis. (Pubmed Central) - Mar 9, 2022 Using autophagy inhibitor 3-MA and inducer compound rapamycin, we found that autophagy negatively regulated the survival, migration, and invasion of synovial cells...Moreover, injection of IL-36 can improve the symptoms of RA in a rat model of RA. Taken together, we conclude that IL-38 and IL-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in RA.
- |||||||||| Journal: The protein level of the tumor-promoting factor SET is regulated by cell density. (Pubmed Central) - Mar 9, 2022
The decrease in SET level due to the loss of SETBP1 was more pronounced in wild-type cells than that in autophagy-deficient cells. These results have revealed a mechanism underlying the regulation of SET level, wherein increased cell density induces SETBP1 expression and protects SET from autophagy.
- |||||||||| GSK-3ALPHA IN HUNTINGTON’S DISEASE (ONSITE: 131-132) - Mar 9, 2022 - Abstract #ADPD2022ADPD_820;
This involves impairment in autophagy, cellular traffic, and membrane transport. The importance of both N/C terminals of GSK-3α in this process suggests that unique protein-protein interactions are required for producing its maximal deleterious effect in boosting mHtt aggregates.
- |||||||||| Sutent (sunitinib) / Pfizer
Mechanism of resistance to the reference anti angiogenic treatment in kidney cancers, sunitinib: Inhibition if autophagy and metabolism adaptation (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_7321; Interestingly, this metabolic adaption sustained proliferation and invasion in cells transiently and chronically exposed to sunitinib but also to other lysosomotropic treatements in different cancer models.Our results highlight original mechanisms associated to the limitations of sunitinib efficacy via a metabolic adaptation of tumor cells and tailoring of the microenvironment. They propose unexplored pathways that may be targeted for patients confronted to therapeutic impasses.
- |||||||||| Anti-hypertensive drugs increase TRAIL sensitivity-induced surface DR5 via autophagy inhibition pathway in prostate cancer cells (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_7194;
Furthermore, the Regulation of DR5 expression was mediated by autophagy flux inhibition followed by ARB treatment. Taken together, the results demonstrated that ARB treatment sensitized prostate cancer cells to TRAIL-induced apoptosis via autophagy inhibition and DR5 protein stabilization, and also suggest that the prostate cancer cells of ARB taken-patient may be sensitized to TRAIL-mediated apoptosis, and may support the mechanism of cohort study which showed reduction of prostate cancer risk ratio in patient taking angiotensin II type 1 receptor blockers.
- |||||||||| Tumor stem cell derived asymmetric dimethylarginine drives immune evasion via functional modulation of macrophages (Section 13) - Mar 9, 2022 - Abstract #AACR2022AACR_6252;
Similarly, IFN-r enhances the proteasomal degradation and inhibition of the proteasomal pathway also reduces the ADMA production induced by IFN-r. In summary, our work shows that tumor (stem) cells may escape from immune surveillance (such as their exposure to activated T lymphocytes or to cytotoxic cytokine, IFN-r) through the secretion of ADMA generated via both autophagic and proteasomal pathways.
- |||||||||| High levels of potassium impair myeloid-derived suppressor cell functions (Section 11) - Mar 9, 2022 - Abstract #AACR2022AACR_5748;
Collectively, this study provides evidence that high levels of potassium change the cellular metabolism of MDSC, reduce their immunosuppressive capacity, impair the signaling of AMPK, C/EBP-β, and promote autophagy. This may provide novel insights for further investigation on the impact of hyperkalemia or microenvironments with increased levels of potassium, such as intratumorally, on MDSCs and their role on tumor growth.
- |||||||||| JNK-IN-8 - Dana-Farber Cancer Institute, University of North Carolina / Chapel Hill
Effects of JNK/Jun blockade on breast cancer cell autophagy are dependent on breast cancer subtype (Section 5) - Mar 9, 2022 - Abstract #AACR2022AACR_5545; Ongoing studies are aimed at understanding the underlying mechanisms of the differential effects of JNK/Jun signaling on autophagy in TNBC versus ERα expressing breast cancer. Such an understanding should provide important information to aid in the ongoing interest in utilizing JNK1/2 as a molecular target for improved treatment of TNBC.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
The effects of autophagy inhibition on HNSCC sensitivity to CTX (Section 5) - Mar 9, 2022 - Abstract #AACR2022AACR_5542; The addition of the autophagy inhibitor SAR405 improved response to CTX treatment. The promising results obtained thus far open the door to future studies investigating the efficacy of combining CTX with more specific autophagy inhibitors.
- |||||||||| ADU-S100 / Chinook Therap
VPS34 inhibitor SB02024 activates cGAS-STING signaling and sensitizes tumors to STING agonist (Section 40) - Mar 9, 2022 - Abstract #AACR2022AACR_4123; Furthermore, combination treatment of VPS34 inhibitor SB02024 with STING agonist ADU-S100 or cGAMP increased the mRNA expression and release of proinflammatory cytokines in human and murine RCC and melanoma cancer cell lines...Taken together, our data demonstrates that targeting of VPS34 results in a cGAS/STING-mediated increase of pro-inflammatory cytokine secretion and synergizes with a STING agonist. We believe that systemic VPS34 inhibition using SB02024 would be of major interest in combination or as an alternative to STING agonists to improve anti-tumor immune responses.
- |||||||||| 5-fluorouracil / Generic mfg., gemcitabine / Generic mfg.
Mechanical stress activates autophagy to induce drug resistance in pancreatic cancer cells (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_3716; In both cases, cells are exposed to the most common chemotherapeutic agents used for pancreatic cancer treatment, gemcitabine and 5-Fluorouracil (5FU). Our results provide solid evidence that alleviation of intratumoral mechanical stresses with mechanotherapeutics combined with autophagy inhibitors can improve the efficacy of chemotherapeutic agents in pancreatic cancer.
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