ArticleCell death & disease2014
Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
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- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Inhibition of STIM1 alleviates high glucose-induced proliferation and fibrosis by inducing autophagy in mesangial cells.Molecular and cellular biochemistry · 2024Article
- Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.Frontiers in cell and developmental biology · 2024Review
- Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases.The Journal of clinical investigation · 2023Article
- STIM1 in tumor cell death: angel or devil?Cell death discovery · 2023Review
- TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination.Journal of experimental & clinical cancer research : CR · 2023Article
- ARL-17477 is a dual inhibitor of NOS1 and the autophagic-lysosomal system that prevents tumor growth in vitro and in vivo.Scientific reports · 2023Article
- The role of extended synaptotagmin at membrane contact sites in cancer research.Frontiers in cell and developmental biology · 2023Review
- Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase.Journal of Cancer · 2023Article
- Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation.Aging cell · 2022Article
- Ion Channels and Transporters in Autophagy.Autophagy · 2022Article
- Article
- Lysosomal agents inhibit store-operated CaJournal of cell science · 2021Article
- Store-Operated Calcium Channels as Drug Target in Gastroesophageal Cancers.Frontiers in pharmacology · 2021Review
- Development of Store-Operated Calcium Entry-Targeted Compounds in Cancer.Frontiers in pharmacology · 2021Review
- Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.International journal of nanomedicine · 2021Review
- Role of Calcium Signaling in Prostate Cancer Progression: Effects on Cancer Hallmarks and Bone Metastatic Mechanisms.Cancers · 2020Review
- Target Molecules of STIM Proteins in the Central Nervous System.Frontiers in molecular neuroscience · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' compound that stimulates autophagosome formation (by downregulating Akt/mammalian target of rapamycin (mTOR) pathway) and inhibits their degradation (by acting like a lysosomotropic agent and increasing lysosomal pH). We show that ML-9 as a monotherapy effectively induces prostate cancer cell death associated with the accumulation of autophagic vacuoles. Further, ML-9 enhances the anticancer activity of docetaxel, suggesting its potential application as an adjuvant to existing anticancer chemotherapy. Altogether, our results revealed the complex effect of ML-9 on autophagy and indentified ML-9 as an attractive tool for targeting autophagy in cancer therapy through dual inhibition of both the Akt pathway and the autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.