ArticleOncotarget2014
Inhibition of the vacuolar ATPase induces Bnip3-dependent death of cancer cells and a reduction in tumor burden and metastasis.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 53 citations in OpenAlex.
- Anti-Cancer Strategy Based on Changes in the Role of Autophagy Depending on the Survival Environment and Tumorigenesis Stages.Molecules (Basel, Switzerland) · 2024Review
- The V-ATPases in cancer and cell death.Cancer gene therapy · 2022Review
- NAMPT Inhibition Induces Neuroblastoma Cell Death and Blocks Tumor Growth.Frontiers in oncology · 2022Article
- Autophagy Modulators in Cancer: Focus on Cancer Treatment.Life (Basel, Switzerland) · 2021Review
- Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts.Disease models & mechanisms · 2021Article
- Role of the V1G1 subunit of V-ATPase in breast cancer cell migration.Scientific reports · 2021Article
- Small Extracellular Vesicles: A Novel Avenue for Cancer Management.Frontiers in oncology · 2021Review
- BNIP3 contributes to cisplatin-induced apoptosis in ovarian cancer cells.FEBS open bio · 2020Article
- Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell Proliferation.Molecular cell · 2020Article
- Differential regulation of AMP-activated protein kinase in healthy and cancer cells explains why V-ATPase inhibition selectively kills cancer cells.The Journal of biological chemistry · 2019Article
- Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer.Cancer medicine · 2018Review
- The V-ATPase subunit A is essential for salt tolerance through participating in vacuolar NaPlanta · 2017Article
- Melatonin enhances sorafenib actions in human hepatocarcinoma cells by inhibiting mTORC1/p70S6K/HIF-1α and hypoxia-mediated mitophagy.Oncotarget · 2017Article
- Article
- Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy.BioImpacts : BI · 2017Review
- Article
- Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy.Frontiers in pharmacology · 2017Review
- Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways.Scientific reports · 2016Article
- Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells.Oncogene · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The pro-apoptotic protein Bnip3 is induced by hypoxia and is present in the core regions of most solid tumors. Bnip3 induces programmed necrosis by an intrinsic caspase independent mitochondrial pathway. Many tumor cells have evolved pathways to evade Bnip3-mediated death attesting to the physiological relevance of the survival threat imposed by Bnip3. We have reported that acidosis can trigger the Bnip3 death pathway in hypoxic cells therefore we hypothesized that manipulation of intracellular pH by pharmacological inhibition of the vacuolar (v)ATPase proton pump, a significant pH control pathway, may activate Bnip3 and promote death of hypoxic cells within the tumor. Here we confirm that bafilomycin A1 (BafA1), a selective vATPase inhibitor, significantly increased death of breast cancer cells in a hypoxia and Bnip3-dependent manner and significantly reduced tumor growth in MCF7 and MDA-MB-231 mouse xenografts. Combined treatment of cells with BafA1 and the ERK1/2 inhibitor U0126 further augmented cell death. Combined treatment of mice containing MDA-MB-231 xenografts with BafA1 and the ERK1/2 inhibitor sorafenib was superior to either treatment alone and supported tumor regression. BafA1 and sorafenib treatments alone reduced MDA-MB-231 cell metastasis and again the combination was significantly more effective than either treatment alone and was without apparent side effects. These results present a novel mechanism to destroy hypoxic tumor cells that may help reverse the resistance of hypoxic tumors to radiation and chemotherapy and perhaps target tumor stem cells.
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.