ArticleBMC cancer2016
Molecular features of the cytotoxicity of an NHE inhibitor: Evidence of mitochondrial alterations, ROS overproduction and DNA damage.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- NHE1-Mediated Metabolic Reprogramming in Cancer.Metabolites · 2026Review
- Associations between four insulin resistance (IR) surrogates and the risk of small cell lung cancer (SCLC).Scientific reports · 2025Article
- Ellipticine targets FGFR3 to mediate the RAS/MAPK-P38 signalling pathway to induce apoptosis in hepatocellular carcinoma cells.3 Biotech · 2025Article
- Application of Composite Soaking Solution in Fillet Storage and Caco-2 Cell Antioxidant Repair.Foods (Basel, Switzerland) · 2025Article
- Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Autophagy and autophagic cell death in sepsis: friend or foe?Journal of intensive care · 2024Review
- NLRP4 renders pancreatic cancer resistant to olaparib through promotion of the DNA damage response and ROS-induced autophagy.Cell death & disease · 2024Article
- Mechanisms of ingested polystyrene micro-nanoplastics (MNPs) uptake and translocation in an in vitro tri-culture small intestinal epithelium.Journal of hazardous materials · 2024Article
- Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia.iScience · 2024Article
- Insulin resistance in NSCLC: unraveling the link between development, diagnosis, and treatment.Frontiers in endocrinology · 2024Review
- Non-Canonical Programmed Cell Death in Colon Cancer.Cancers · 2022Review
- Mulberry Ethanol Extract and Rutin Protect Alcohol-Damaged GES-1 Cells by Inhibiting the MAPK Pathway.Molecules (Basel, Switzerland) · 2022Article
- DNA damage and metabolic mechanisms of cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species.International journal of molecular sciences · 2021Article
- The Antifungal Activity of HMA, an Amiloride Analog and Inhibitor of NaFrontiers in microbiology · 2021Article
- Pyrazine ring-based NaScientific reports · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNH exchangers (NHEs) play a crucial role in regulating intra/extracellular pH, which is altered in cancer cells, and are therefore suitable targets to alter cancer cell metabolism in order to inhibit cell survival and proliferation. Among NHE inhibitors, amiloride family members are commonly used in clinical practice as diuretics; we focused on the amiloride HMA, reporting a net cytotoxic effect on a panel of human cancer cell lines; now we aim to provide new insights into the molecular events leading to cell death by HMA.
methodsColon cancer cell lines were treated with HMA and analysed with: morphological and cellular assays for cell viability and death, and autophagy; biochemical approaches to evaluate mitochondrial function and ROS production; in situ detection of DNA damage; molecular tools to silence crucial autophagy/necroptosis factors.
resultsHMA affects cellular morphology, alters mitochondrial structure and function, causes an increase in ROS, which is detrimental to DNA integrity, stimulates poly(ADP-ribose) synthesis, activates RIPK3-dependent death and triggers autophagy, which is unable to rescue cell survival. These features are hot points of an intricate network of processes, including necroptosis and autophagy, regulating the homeostasis between survival and death.
conclusionOur results allow the identification of multiple events leading to cell death in cancer cells treated with HMA. The here-defined intricate network activated by HMA could be instrumental to selectively target the key players of each pathway in the attempt to improve the global response to HMA. Our data could be the starting point for developing a newly designed targeted therapy.
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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.