ArticlePloS one2013
A cell-permeant amiloride derivative induces caspase-independent, AIF-mediated programmed necrotic death of breast cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Select novel small-molecule uPA potential inhibitors as anti-cancer agents against breast cancer.Scientific reports · 2026Article
- Apoptosis-inducing factor (AIF) at the crossroad of cell survival and cell death: implications for cancer and mitochondrial diseases.Cell communication and signaling : CCS · 2025Review
- A novel lipophilic amiloride derivative efficiently kills chemoresistant breast cancer cells.Scientific reports · 2024Article
- Article
- A RIPK3-independent role of MLKL in suppressing parthanatos promotes immune evasion in hepatocellular carcinoma.Cell discovery · 2023Article
- The epithelial sodium channel has a role in breast cancer cell proliferation.Breast cancer research and treatment · 2021Article
- Corilagin inhibits breast cancer growth via reactive oxygen species-dependent apoptosis and autophagy.Journal of cellular and molecular medicine · 2018Article
- Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo.BMC cancer · 2017Article
- Molecular features of the cytotoxicity of an NHE inhibitor: Evidence of mitochondrial alterations, ROS overproduction and DNA damage.BMC cancer · 2016Article
- Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy.Oncotarget · 2016Review
- RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Hexamethylene amiloride engages a novel reactive oxygen species- and lysosome-dependent programmed necrotic mechanism to selectively target breast cancer cells.Cancer letters · 2016Article
- Data integration to prioritize drugs using genomics and curated data.BioData mining · 2016Article
- Mis-trafficking of endosomal urokinase proteins triggers drug-induced glioma nonapoptotic cell death.Molecular pharmacology · 2015Article
- β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.Cell death & disease · 2014Article
- Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor.Molecular cancer · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Amiloride is a potassium-sparing diuretic that has been used as an anti-kaliuretic for the chronic management of hypertension and heart failure. Several studies have identified a potential anti-cancer role for amiloride, however the mechanisms underlying its anti-tumor effects remain to be fully delineated. Our group previously demonstrated that amiloride triggers caspase-independent cytotoxic cell death in human glioblastoma cell lines but not in primary astrocytes. To delineate the cellular mechanisms underlying amiloride's anti-cancer cytotoxicity, cell permeant and cell impermeant derivatives of amiloride were synthesized that exhibit markedly different potencies in cancer cell death assays. Here we compare the cytotoxicities of 5-benzylglycinyl amiloride (UCD38B) and its free acid 5-glycinyl amiloride (UCD74A) toward human breast cancer cells. UCD74A exhibits poor cell permeability and has very little cytotoxic activity, while UCD38B is cell permeant and induces the caspase-independent death of proliferating and non-proliferating breast cancer cells. UCD38B treatment of human breast cancer cells promotes autophagy reflected in LC3 conversion, and induces the dramatic swelling of the endoplasmic reticulum, however these events do not appear to be the cause of cell death. Surprisingly, UCD38B but not UCD74A induces efficient AIF translocation from the mitochondria to the nucleus, and AIF function is necessary for the efficient induction of cancer cell death. Our observations indicate that UCD38B induces programmed necrosis through AIF translocation, and suggest that its cytosolic accessibility may facilitate drug action.
Indexed as
Identifiers
What OpenQuestion holds
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.