- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines. (Pubmed Central) - Sep 28, 2023 ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine)...Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.
- |||||||||| Journal: Ubiquitin Ligase Nrdp1 Controls Autophagy-Associated Acrosome Biogenesis and Mitochondrial Arrangement during Spermiogenesis. (Pubmed Central) - Sep 28, 2023
Deletion of Nrdp1 increased the levels of Parkin but decreased the levels of SIP, the mitochondrial fission protein Drp1 and the mitochondrial protein Tim23 in sperm, accompanied by the inhibition of autophagy, the impairment of acrosome biogenesis and the disruption of mitochondrial arrangement in sperm. Thus, our results uncover an essential role of Nrdp1 in spermiogenesis and male fertility by promoting autophagy, providing important clues to cope with the related male reproductive diseases.
- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: Hydroxyproline metabolism enhances IFN-?-induced PD-L1 expression and inhibits autophagic flux. (Pubmed Central) - Sep 25, 2023
Mechanistic studies reveal that Hyp acts as an inhibitor of autophagic flux, which allows it to regulate this negative feedback mechanism, thereby contributing to its overall effect on PD-L1 expression. Due to its prevalence in fibrotic tumors, these findings suggest that hydroxyproline could contribute to the establishment of an immunosuppressive tumor microenvironment and that Hyp metabolism could be targeted to pharmacologically control PD-L1 expression for the treatment of cancer or autoimmune diseases.
- |||||||||| Review, Journal: Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection. (Pubmed Central) - Sep 23, 2023
Mycobacterium tuberculosis's unique autophagy-blocking capability makes it challenging to eliminate compared to usual pathogens. The present review discusses recent advances in autophagy-inhibiting factors and mechanisms that could be exploited to identify autophagy-inducing chemotherapeutics that could be used as adjunctive therapy with the existing first-line anti-TB agent to shorten the duration of therapy and enhance cure rates from multidrug-resistant tuberculosis (MDR-TB) and extreme drug-resistant tuberculosis (XDR-TB).
- |||||||||| Tavegil (clemastine) / GSK
Preclinical, Journal: Clemastine fumarate attenuates tauopathy and meliorates cognition in hTau mice via autophagy enhancement. (Pubmed Central) - Sep 22, 2023 Notably, after administration of chloroquine, levels of Tau protein were significantly increased. When clemastine fumarate was co-administered with chloroquine, the protective effects were reversed, indicating that clemastine fumarate indeed triggered autophagy and promoted the degradation of Tau protein, while also inhibiting further Tauopathy-related neuroinflammation and synapse loss to improve cognitive function in hTau mice.
- |||||||||| Biomarker, Journal: A prognostic biomarker NRG1 promotes U-87 MG glioblastoma cell malignancy by inhibiting autophagy via ERBB2/AKT/mTOR pathway. (Pubmed Central) - Sep 22, 2023
In vitro experiments showed that NRG1 promoted U87 cell migration and proliferation by inhibiting autophagy, and ERBB2/AKT/mTOR is a downstream pathway that mediates the autophagy-inhibitory effects of NRG1. We constructed an ATG gene prognostic model for GBM and demonstrated that NRG1 inhibited autophagy by activating ERBB2/AKT/mTOR, promoting GBM malignancy, thus providing new insights into the molecular contribution of autophagy in GBM malignancy.
- |||||||||| colchicine / Generic mfg.
Angiotensin II-Mediated Suppression of Skeletal Muscle Autophagy via mTOR and FoxO3a Pathways (Zone 1, Science and Technology Hall, Level 2) - Sep 21, 2023 - Abstract #AHA2023AHA_7992; Suppression of autophagy via these pathways likely disrupts clearance of damaged MT, leading to SK.M atrophy. These results provide insights for future development of therapies for CHF-induced cachexia by targeting mTOR and FoxO3a pathways to restore autophagy.
- |||||||||| lapatinib / Generic mfg.
Preclinical, Journal: Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models. (Pubmed Central) - Sep 21, 2023 Preliminary in vitro data generated using a parallel artificial membrane permeability (PAMPA) assay suggested that Rhiz cannot cross the blood brain barrier and therefore alternative drug delivery methods should be used in the further in vivo studies. In conclusion, Rhiz is a promising new candidate for the treatment of human glioblastoma, which should be further developed in combination with EGFR inhibitors.
- |||||||||| dactolisib (RTB101) / Adicet Bio
Journal: Synergistic effect of Dactolisib/Lys05 combination on autophagy in A549 cells. (Pubmed Central) - Sep 21, 2023 A549 cells treated in a 2:1 ratio of Lys05 and Dactolisib demonstrated a synergistic effect on cell death, proliferation, and apoptotic gene markers, in addition to its effect on autophagic gene and protein markers, showing an enhanced effect compared to monotherapy. Therefore, the PI3K/AKT kinase inhibitor/autophagy inhibitor combination establishes higher therapeutic benefits on A549 cells compared to kinase inhibitor monotherapy.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
INHIBITION OF AUTOPHAGY ENHANCES THE ANTI?TUMOR EFFECTS ON THYROID CANCER () - Sep 20, 2023 - Abstract #ATA2023ATA_426; Inhibiting autophagy chemically or genetically enhanced lenvatinib's cytotoxic effects and anti?angiogenic efficacy in thyroid cancer cells in vitro and in vivo.In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, autophagy inhibition can enhance the antitumor effect offered by Lenvatinib, which may represent a novel and effective treatment option for PTC to overcome drug resistance.
- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal, PARP Biomarker, IO biomarker: Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model. (Pubmed Central) - Sep 19, 2023 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.
- |||||||||| Review, Journal: mTOR signaling and Alzheimer's disease: What we know and where we are? (Pubmed Central) - Sep 18, 2023
Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms.
- |||||||||| Tasigna (nilotinib) / Novartis, Inhibikase
Journal: Chloroquine Intervenes Nephrotoxicity of Nilotinib through Deubiquitinase USP13-Mediated Stabilization of Bcl-XL. (Pubmed Central) - Sep 18, 2023 Additionally, it is found that USP13 abrogates cell apoptosis by preventing excessive ubiquitin-proteasome degradation of Bcl-XL. In conclusion, the research reveals the molecular mechanism of nilotinib's nephrotoxicity, highlighting USP13 as an important regulator of Bcl-XL stability in determining cell fate, and provides CQ analogs as a clinical intervention strategy for nilotinib's nephrotoxicity.
- |||||||||| cisplatin / Generic mfg.
Journal, Cancer stem: Co-targeting autophagy and NRF2 signaling triggers mitochondrial superoxide to sensitize oral cancer stem cells for cisplatin-induced apoptosis. (Pubmed Central) - Sep 18, 2023 Genetic inhibition of NRF2 (siNRF2) in autophagy-deficient CD44 cells increases mtROS level, reducing cisplatin-resistance CSCs, and pre-treatment with mitoTEMPO [a mitochondria-targeted SOD (superoxide dismutase) mimetic] lessened the cytotoxic effect enhancing cancer stemness. We also found that inhibiting autophagy (with CQ) and NRF2 signaling (with ML-385) combinedly increased cisplatin cytotoxicity, thereby suppressing the expansion of oral CD44 cells; this finding has the potential to be clinically applicable in resolving CSC-associated chemoresistance and tumor relapse in oral cancer.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal, IO biomarker: Panax notoginseng saponins inhibits oxidative stress- induced human nucleus pulposus cell apoptosis and delays disc degeneration in vivo and in vitro. (Pubmed Central) - Sep 16, 2023 We also found that inhibiting autophagy (with CQ) and NRF2 signaling (with ML-385) combinedly increased cisplatin cytotoxicity, thereby suppressing the expansion of oral CD44 cells; this finding has the potential to be clinically applicable in resolving CSC-associated chemoresistance and tumor relapse in oral cancer. Our study showed that PNS could protect HNP cells against apoptosis via autophagy inhibition and ameliorate disc degeneration in vivo, indicating its potential to be a therapeutic agent for IDD.
- |||||||||| Journal: Evidence that the domesticated fungus Leucoagaricus gongylophorus recycles its cytoplasmic contents as nutritional rewards to feed its leafcutter ant farmers. (Pubmed Central) - Sep 16, 2023
We next confirmed that autophagy plays a critical role in gongylidium formation both: (1) in vitro as gongylidium suppression occurred when isolated fungal cultures were grown on media with autophagy inhibitors, and (2) in silico as differential transcript expression (RNA-seq) analyses showed upregulation of multiple autophagy gene isoforms in gongylidia relative to undifferentiated hyphae. While autophagy is a ubiquitous and often highly derived process across the tree of life, our study reveals a new role for autophagy as a mechanism of functional integration between ant farmers and their fungal crop, and potentially as a signifier of higher-level homeostasis between uniquely life-time committed ectosymbionts.
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