ArticleOncotarget2016
The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
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- Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor.Marine drugs · 2023Article
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- Targeting mitochondrial ion channels for cancer therapy.Redox biology · 2021Review
- Acacetin Protects Myocardial Cells against Hypoxia-Reoxygenation Injury through Activation of Autophagy.Journal of immunology research · 2021Article
- Role of Sodium/Calcium Exchangers in Tumors.Biomolecules · 2020Review
- Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis.Science advances · 2020Article
- Sodium homeostasis in the tumour microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2019Review
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- Identification of compound CA-5f as a novel late-stage autophagy inhibitor with potent anti-tumor effect against non-small cell lung cancer.Autophagy · 2019Article
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- Role of the MAPK/cJun NHAutophagy · 2018Article
- Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We explored the effects of KB-R7943, an inhibitor of reverse-mode NCX1 activity, in prostate cancer (PCa). NCX1 was overexpressed in PCa tissues and cell lines, and higher NCX1 levels were associated higher PCa grades. At concentrations greater than 10 μM, KB-R7943 dose-dependently decreased PC3 and LNCaP cell viability. KB-R7943 also increased cell cycle G1/S phase arrest and induced apoptosis in PC3 cells. KB-R7943 increased autophagosome accumulation in PCa cells as indicated by increases in LC3-II levels and eGFP-LC3 puncta. Combined treatment with chloroquine (CQ) and KB-R7943 decreased P62 and increased LC3-II protein levels in PC3 cells, indicating that KB-R7943 blocked autophagic flux. KB-R7943 induced autophagosome accumulation mainly by downregulating the PI3K/AKT/m-TOR pathway and upregulating the JNK pathway. In xenograft experiments, KB-R7943 inhibited tumor growth. Combined treatment with KB-R7943 and an autophagy inhibitor inhibited growth and increased apoptosis. These results indicate that KB-R7943 promotes cell death in PCa by activating the JNK signaling pathway and blocking autophagic flux.
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