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.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Kondratskyi A,Yassine M,Slomianny C,Kondratska K,Gordienko D,Dewailly E,Lehen'kyi V,Skryma R,Prevarskaya Ndoi
10.1038/cddis.2014.156subject
Has Abstractpub_date
2014-04-24 00:00:00pages
e1193issn
2041-4889pii
cddis2014156journal_volume
5pub_type
杂志文章abstract::Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging br...
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journal_title:Cell death & disease
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更新日期:2017-10-05 00:00:00
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pub_type: 杂志文章
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pub_type: 已发布勘误
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pub_type: 临床试验,杂志文章
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abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...
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journal_title:Cell death & disease
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abstract::Mammalian folliculogenesis is a complex process in which primordial follicles develop into pre-ovulatory follicles, followed by ovulation to release mature oocytes. In this study, we explored the role of miR-144 in ovulation. miR-144 was one of the differentially expressed microRNAs, which showed 5.59-fold changes, in...
journal_title:Cell death & disease
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abstract::Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial...
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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