- |||||||||| hydroxychloroquine / Generic mfg.
PK/PD data, Journal: Pharmacokinetic and Pharmacodynamic Assessment of Hydroxychloroquine in Breast Cancer. (Pubmed Central) - Dec 31, 2021 Significance Statement Autophagy dependent tumors, but not autophagy independent tumors, have decreased cell proliferation and increased cell death following single agent hydroxychloroquine treatment. However, hydroxychloroquine causes decreased autophagic flux regardless of autophagy status, suggesting its clinical efficacy in the context of autophagy inhibition.
- |||||||||| Journal, IO biomarker: Pyoluteorin Induces Apoptosis and Autophagy in NSCLC Cells. (Pubmed Central) - Dec 30, 2021
Our results showed that pyoluteorin could induce both apoptosis and autophagy in human NSCLC cells. Combination of pyoluteorin with autophagy inhibitior significantly promoted pyoluteorin-induced apoptosis and may be a potential anticancer strategy in the NSCLC therapy.
- |||||||||| sirolimus / Generic mfg.
Journal: Impaired Autophagy Induced by oxLDL/β2GPI/anti-β2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction. (Pubmed Central) - Dec 30, 2021 Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine...3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction...Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.
- |||||||||| icaritin (SNG-162) / Shenogen Pharma
Journal: The antitumor effects of icaritin against breast cancer is related to estrogen receptors. (Pubmed Central) - Dec 29, 2021 The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy. Our study demonstrated that the antitumor effects of icaritin against breast cancer are related with ER, which suggested that the status of ER should be considered in clinical application of icaritin.
- |||||||||| SCH-23390 / Boehringer Ingelheim
Journal: Dopamine D receptor-mediated decreases in mitochondrial reactive oxygen species production are cAMP and autophagy dependent. (Pubmed Central) - Dec 29, 2021 By contrast, Sch23390, a DR and DR antagonist, increased mito-ROS production in the absence of DR, DR is constitutively active...In the presence of chloroquine or spautin-1, inhibitors of autophagy, fenoldopam further increased ATG5 and LC3-II expression, indicating an important role of DR in the positive regulation of autophagy...Moreover, ROS production was increased in mitochondria isolated from the kidney cortices of Drd5 mice, relative to Drd5 littermates. In conclusion, DR-mediated activation of autophagy plays a role in the DR-mediated inhibition of mito-ROS production in the kidneys.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats. (Pubmed Central) - Dec 29, 2021 Consistently, the activation and inhibition of autophagy using rapamycin and LY294002 confirmed the regulatory effects of 11R‑VIVIT on autophagy. On the whole, the findings of the present study demonstrate that 11R‑VIVIT promotes fracture healing in osteoporotic rats and enhances the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway.
- |||||||||| Journal: Defective transcription elongation in human cancers imposes targetable proteotoxic vulnerability. (Pubmed Central) - Dec 28, 2021
As such, while these cells were highly resistant to proteasome inhibitors, they were acutely sensitive to inhibitors of autophagy in vitro and in vivo. This study reveals a major aberrant phenotype that is observed in ∼15-25% of all cancers and characterizes a unique cellular vulnerability that can be readily exploited in the clinic to improve treatment efficacy.
- |||||||||| selisistat (SEN-196) / AOP Orphan Pharma
Journal, IO biomarker: L-Arginine protects cementoblasts against hypoxia-induced apoptosis through Sirt1-enhanced autophagy. (Pubmed Central) - Dec 28, 2021 Similarly, L-arg upregulated Sirt1, which activated autophagy in the root resorption model, and less root resorption was observed in the Sirt1 activation group. CONCLUSION(S): : L-arg reduced cementoblast apoptosis in hypoxia and reduced root resorption induced by loading force in rats, which may be partly mediated by Sirt1-enhanced autophagy.
- |||||||||| sirolimus / Generic mfg.
Journal: Curcumol simultaneously induces both apoptosis and autophagy in human nasopharyngeal carcinoma cells. (Pubmed Central) - Dec 28, 2021 In contrast, combining curcumol with autophagy agonist rapamycin and apoptosis inducer MG132 synergized the apoptotic and autophagic effect of curcumol. Taken together, our study demonstrates that curcumol promotes autophagy in NPC via AMPK/mTOR pathway, induces autophagy enhances the activity of curcumol in NPC cells; the combination of autophagy inducer and curcumol can be a new therapeutic strategy for NPC.
- |||||||||| Review, Journal: HDAC6 Inhibition Extinguishes Autophagy in Cancer: Recent Insights. (Pubmed Central) - Dec 27, 2021
We focus on the controversy surrounding their ability to promote or block tumor progression and explore the impact of HDAC6 inhibitors on autophagy modulation in cancer. In light of the fact that targeted drug therapy for cancer patients is attracting ever increasing interest within the research community and in society at large, we discuss the possibility of using HDAC6 inhibitors as adjuvants and/or in combination with conventional treatments to overcome autophagy-related mechanisms of resistance.
- |||||||||| Review, Journal: The Implication of Autophagy in Gastric Cancer Progression. (Pubmed Central) - Dec 27, 2021
The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.
- |||||||||| Review, Journal: Mechanisms of FA-Phagy, a New Form of Selective Autophagy/Organellophagy. (Pubmed Central) - Dec 27, 2021
This paper mainly reviews the cargo recognition mechanisms of FA-phagy (selective autophagy-mediated FA turnover) and its disease relevance. We seek to outline some new points of understanding that will facilitate further study of FA-phagy and precise therapeutic strategies for related diseases associated with aberrant FA functions.
- |||||||||| selisistat (SEN-196) / AOP Orphan Pharma
Journal, IO biomarker: Rhein inhibits hydrogen peroxide-induced apoptosis of human umbilical vein endothelial cells and its mechanism (Pubmed Central) - Dec 27, 2021 The addition of SIRT1 inhibitor EX-527 reduced the protective effect of RH and cell viability...After RH treatment, the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK) increased, while that of the mechanistic target of rapamycin(mTOR) decreased in a dose-dependent manner. Moreover, this effect could be weakened by the AMPK inhibitor compound C. RH may enhance autophagy through SIRT1/AMPK/mTOR pathway to reduce H_2O_2-induced apoptosis of HUVECs.
- |||||||||| Journal: Autophagy receptors as viral targets. (Pubmed Central) - Dec 25, 2021
Pathogens have evolved ways to evade their autophagic degradation to promote their replication, and recent research has shown autophagic receptors to be an important and perhaps previously overlooked target of viral autophagy inhibition. This is a brief summary of the recent progress in knowledge of virus-host interaction in the context of autophagy receptors.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Chrysin induces autophagy through the inactivation of the ROS‑mediated Akt/mTOR signaling pathway in endometrial cancer. (Pubmed Central) - Dec 25, 2021 Furthermore, the inhibition of autophagy by chloroquine enhanced the inhibitory effect on cell proliferation and the promotion of the chrysin‑induced apoptosis of EC cells, indicating that chrysin‑induced autophagy was a cytoprotective mechanism...Furthermore, the phosphorylated (p‑)Akt and p‑mTOR levels were significantly decreased in a concentration‑dependent manner following treatment with chrysin, while NAC blocked these effects. Taken together, these findings demonstrated that chrysin‑induced autophagy via the inactivation of the ROS‑mediated Akt/mTOR signaling pathway in EC cells.
- |||||||||| Journal: The autophagy protein ATG9A enables lipid mobilization from lipid droplets. (Pubmed Central) - Dec 25, 2021
ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes.
- |||||||||| deoxyglucose / Generic mfg.
Journal: A requirement for autophagy in HMGA2-induced metabolic reprogramming to support Cd-induced migration. (Pubmed Central) - Dec 23, 2021 2-Deoxy-d-glucose (2DG, 5 mM), the inhibitor of glycolysis decreased Cd/HMGA2-induced cell migration and restored Cd/HMGA2-decreased OXPHOS and mitochondrial mass...Overall, our study demonstrated that autophagy was required for HMGA2-mediated metabolic reprogramming, which was critical for Cd-induced migration. Targeting HMGA2 and autophagy-dependent reprogrammed metabolism may be an effective way to inhibit Cd-induced cell migration.
- |||||||||| Journal: Callyspongiolide kills cells by inducing mitochondrial dysfunction via cellular iron depletion. (Pubmed Central) - Dec 23, 2021
Notably, these effects were rescued through iron supplementation. Although our approach was unable to reveal the direct protein targets of callyspongiolide, unique phenomena observed only by TS-FITGE provided critical insight into the mechanism of action of callyspongiolide and specifically its cytotoxic activity via induction of mitochondrial dysfunction through cellular iron depletion caused by lysosomal deacidification, which occurred independent of known programmed cell death pathways.
- |||||||||| Clinical, Review, Journal, IO biomarker: Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer. (Pubmed Central) - Dec 23, 2021
Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy.
- |||||||||| Journal: S100A11 Promotes Liver Steatosis via FOXO1-Mediated Autophagy and Lipogenesis. (Pubmed Central) - Dec 22, 2021
A high-fat diet promotes liver S100A11 expression, which may interact with HDAC6 to block its binding to FOXO1, releasing or increasing the acetylation of FOXO1, thus activating autophagy and lipogenesis, and accelerating lipid accumulation and liver steatosis. These findings indicate a completely novel S100A11-HDAC6-FOXO1 axis in the regulation of autophagy and liver steatosis, providing potential possibilities for the treatment of NAFLD.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health
Journal: ULK1 Inhibition as a Targeted Therapeutic Strategy for Psoriasis by Regulating Keratinocytes and Their Crosstalk With Neutrophils. (Pubmed Central) - Dec 22, 2021 Topical application of SBI0206965, a selective ULK1 inhibitor, significantly attenuated epidermal hyperplasia, infiltration of neutrophils, and transcripts of the psoriasis-related markers in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD)...Our findings suggest a self-regulatory process by downregulating ULK1 to maintain the immune homeostasis of psoriatic skin via regulating keratinocytes and their crosstalk with neutrophils, possibly through both autophagy-dependent and independent mechanisms. ULK1 might be a potential target for preventing or treating psoriasis.
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