- |||||||||| Review, Journal: Autophagy Inhibition in BRAF-Driven Cancers. (Pubmed Central) - Jul 28, 2021
Several mechanisms have been proposed for BRAFi-induced autophagy, such as activation of the endoplasmic reticulum (ER) stress gatekeeper GRP78, AMP-activated protein kinase, and transcriptional regulation of the autophagy regulating transcription factors TFEB and TFE3 via ERK1/2 or mTOR inhibition. This review describes the relationship between BRAF-targeted therapy and autophagy regulation, and discusses possible future treatment strategies of combined inhibition of oncogenic signaling plus autophagy for BRAF-driven cancers.
- |||||||||| chloroquine phosphate / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Babao Dan Reverses Multiple-Drug Resistance in Gastric Cancer Cells via Triggering Apoptosis and Autophagy and Inhibiting PI3K/AKT/mTOR Signaling. (Pubmed Central) - Jul 27, 2021 To determine whether BBD triggers apoptosis and autophagy through the PI3K/AKT/mTOR signaling, we also applied 3-methyladenine (3-MA), chloroquine (CQ), and 740Y-P (an activator of PI3K)...PI3K agonist, 740Y-P, further verified BBD inhibition of PI3K/AKT/mTOR pathway activation. In conclusion, BBD may reverse the MDR of gastric cancer cells, induce apoptosis, and promote autophagy via inactivation of the PI3K/AKT/mTOR signaling pathway.
- |||||||||| Preclinical, Journal: Qingfei oral liquid inhibited autophagy to alleviate inflammation via mTOR signaling pathway in RSV-infected asthmatic mice. (Pubmed Central) - Jul 24, 2021
Furthermore, QF was found to reduce the quantity of autophagy and its related proteins LC3B (light chain 3B), Beclin-1, p62 and Atg5 (autophagy-related gene 5) and downstream inflammatory cytokines TNF-α, IL-4, IL-6, and IL-13 via an action in mTOR-dependent signaling in vivo and in vitro. These findings suggest that QF can alleviate the inflammation caused by RSV infection in asthmatic mice, and its mechanism may be involved in the regulation of autophagy via the mTOR signaling pathway.
- |||||||||| Zolinza (vorinostat) / Merck (MSD)
Journal: Fucoidan induces ROS-dependent epigenetic modulation in cervical cancer HeLa cell. (Pubmed Central) - Jul 24, 2021 In this study, we investigated the effect of Fucoidan on cell viability, redox balance, cytoskeletal component F-actin, HDAC inhibition, autophagy, and senescence phenomenon in human cervical cancer HeLa cell line in comparison to positive control suberoylanilide hydroxamic acid by flow cytometry, fluorescence microscopy, and western blotting...Molecular docking study validates Fucoidan-HDAC1 association in corroboration with the experimental data. Collectively, these mechanistic studies demonstrated that Fucoidan could be a therapeutic molecule for targeting HDACs in cervical cancer.
- |||||||||| Journal: Narciclasine attenuates sepsis-induced myocardial injury by modulating autophagy. (Pubmed Central) - Jul 23, 2021
Importantly, narciclasine exerted an inhibitory effect on the JNK signaling pathway, and JNK activity was tightly associated with narciclasine-induced autophagy and the consequent protective effects during AMI. Taken together, our findings indicate that narciclasine protects against LPS-induced AMI by inducing JNK-dependent autophagic flux; hence, narciclasine may be an effective and novel agent for the clinical treatment of sepsis-induced myocardial injury.
- |||||||||| Journal: Alpha-lipoic acid inhibits lung cancer growth via mTOR-mediated autophagy inhibition. (Pubmed Central) - Jul 22, 2021
Inhibition of mTOR with rapamycin reversed LA-induced inactivation of autophagy and abolished LA-induced suppression of A549 cell viability. Altogether, the data suggest that LA exerts an anti-lung cancer effect through mTOR-mediated inhibition of autophagy, and thus LA may have therapeutic potential for lung cancer management.
- |||||||||| Journal: Autophagosome Trafficking. (Pubmed Central) - Jul 22, 2021
F-actin-depolymerizing drugs, which inhibit autophagosome formation, and also subsequently inhibit autophagosome trafficking 3. Motor protein regulators, which directly affect autophagosome trafficking.
- |||||||||| dexmedetomidine / Generic mfg.
Journal: Dexmedetomidine Protects Against Oxygen-Glucose Deprivation-Induced Injury Through Inducing Astrocytes Autophagy via TSC2/mTOR Pathway. (Pubmed Central) - Jul 21, 2021 In addition, DEX enhanced the expression of tuberous sclerosis complex 2 (TSC2) in primary cultured astrocytes, while reduced the expression of mammalian target of rapamycin (mTOR). In conclusion, our study suggests that DEX exerts a neuroprotection against OGD-induced astrocytes injury via activation of astrocytes autophagy by regulating the TSC2/mTOR signaling pathway, which provides a new insight into the mechanisms of DEX treatment for acute ischemic injury.
- |||||||||| Journal: Casein kinase 1α inhibits p53 downstream of MDM2‑mediated autophagy and apoptosis in acute myeloid leukemia. (Pubmed Central) - Jul 21, 2021
CK1α interacted with murine double minute 2 (MDM2) and p53, and CK1α inhibitor D4476 significantly upregulated p53 and phosphorylated 5' AMP‑activated protein kinase (AMPK), and substantially inhibited the phosphorylation of mammalian target of rapamycin (mTOR). Our findings indicate that CK1α promotes AML by suppressing p53 downstream of MDM2‑mediated autophagy and apoptosis, suggesting that targeting CK1α provides a therapeutic opportunity to treat AML.
- |||||||||| Journal: Autophagy induction promotes renal cyst growth in polycystic kidney disease. (Pubmed Central) - Jul 21, 2021
Our findings indicate that CK1α promotes AML by suppressing p53 downstream of MDM2‑mediated autophagy and apoptosis, suggesting that targeting CK1α provides a therapeutic opportunity to treat AML. Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD.
- |||||||||| Review, Journal: Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy. (Pubmed Central) - Jul 21, 2021
However, the mechanisms of lysosomal/energy stress co-amplification, apart from the protective autophagy inhibition, are poorly understood. We here summarize the established and suggest potential mechanisms and candidates for anticancer therapy based on the dual targeting of lysosomes and energy metabolism.
- |||||||||| metformin / Generic mfg.
Review, Journal: The effects of metformin on autophagy. (Pubmed Central) - Jul 21, 2021 The pharmacological effects of metformin combining its actions on autophagy were also discussed. It would help better apply metformin to treat diseases in term of mediating autophagy.
- |||||||||| Journal: Vascular endothelial cell-secreted exosomes facilitate osteoarthritis pathogenesis by promoting chondrocyte apoptosis. (Pubmed Central) - Jul 21, 2021
Through in vivo and in vitro experiments, we demonstrated that exosomes derived from vascular endothelial cells decreased the ability of chondrocytes to resist oxidative stress by inhibiting autophagy and p21 expression, thereby increasing the cellular ROS content and inducing apoptosis. These findings indicate that exosomes derived from vascular endothelial cells promote the progression of OA, thus, providing new ideas for the diagnosis and treatment of OA.
- |||||||||| niclosamide / Generic mfg.
Journal: SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. (Pubmed Central) - Jul 21, 2021 Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.
- |||||||||| Journal: Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs. (Pubmed Central) - Jul 21, 2021
Using electrophysiology and fluorescent ion imaging of 3a-reconstituted liposomes, we observe Ca-permeable, nonselective cation channel activity, identify mutations that alter ion permeability and discover polycationic inhibitors of 3a activity. 3a-like proteins are found across coronavirus lineages that infect bats and humans, suggesting that 3a-targeted approaches could treat COVID-19 and other coronavirus diseases.
- |||||||||| SB-705498 / GSK
[VIRTUAL] DOPAMINE REGULATES AUTOPHAGY DURING TGF-Β1-INDUCED ACTIVATION OF HEPATIC STELLATE CELLS (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_4733; Dopamine may act as a protective factor in the process of liver fibrosis. Dopamine may activate TRPV1 calcium channel on cell membrane to mediate extracellular calcium influx, leading to intracellular calcium remodeling, and then inhibit the autophagy and activation of HSCs mediated by TGF-β1/Smad3 signaling pathway, and finally play an anti-fibrosis role.
- |||||||||| SB-705498 / GSK
[VIRTUAL] DOPAMINE REGULATES AUTOPHAGY DURING TGF-Β1-INDUCED ACTIVATION OF HEPATIC STELLATE CELLS (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_2553; Dopamine may act as a protective factor in the process of liver fibrosis. Dopamine may activate TRPV1 calcium channel on cell membrane to mediate extracellular calcium influx, leading to intracellular calcium remodeling, and then inhibit the autophagy and activation of HSCs mediated by TGF-β1/Smad3 signaling pathway, and finally play an anti-fibrosis role.
- |||||||||| SB-705498 / GSK
[VIRTUAL] DOPAMINE REGULATES AUTOPHAGY DURING TGF-Β1-INDUCED ACTIVATION OF HEPATIC STELLATE CELLS (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_722; Dopamine may act as a protective factor in the process of liver fibrosis. Dopamine may activate TRPV1 calcium channel on cell membrane to mediate extracellular calcium influx, leading to intracellular calcium remodeling, and then inhibit the autophagy and activation of HSCs mediated by TGF-β1/Smad3 signaling pathway, and finally play an anti-fibrosis role.
- |||||||||| oxaliplatin / Generic mfg.
Journal: A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma. (Pubmed Central) - Jul 17, 2021 The release of OH-MSNs to Oxaliplatin was enhanced under acidic conditions; compared with Oxaliplatin or O-MSNs, OH-MSNs showed more potent killing effects against cholangiocarcinoma cells (P<0.05), and exerted notably inhibitory effects on the activity of cholangiocarcinoma cells (P<0.05), promoted their apoptosis (P<0.05), and greatly facilitated the expression of pro-apoptotic factors and autophagic factors in cholangiocarcinoma cells (P<0.05), and markedly inhibited the expression of anti-apoptotic factors and autophagic inhibitory factors (P<0.05); moreover, OH-MSNs could significantly suppress the growth of mouse cholangiocarcinoma (P<0.05) and induce apoptosis of tumor cells compared with Oxaliplatin or O-MSNs (P<0.05). MSNs loading greatly increases the killing effect of Oxaliplatin on cholangiocarcinoma cells and upgrades the autophagic level of cholangiocarcinoma cells, while OH-MSNs synthesized by further loading HCE6 have a more apparent killing effect on cholangiocarcinoma cells.
|