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Cited by 301

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species

Open access
De Milito, Angelo, Iessi, Elisabetta, Logozzi, Mariantonia, Lozupone, Francesco, Spada, Massimo, Marino, Maria Lucia, Federici, Cristina, Perdicchio, Maurizio, Matarrese, Paola, Lugini, Luana, Nilsson, Anna, Fais, Stefano·2007·Cancer Research
DOI 10.1158/0008-5472.can-06-4095
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Abstract

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI. [Cancer Res 2007;67(11):5408–17]

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Metadata

Authors
De Milito, A., Iessi, E., Logozzi, M., Lozupone, F., Spada, M., Marino, M. L., Federici, C., Perdicchio, M., Matarrese, P., Lugini, L., Nilsson, A., & Fais, S.
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2007-06-01
Volume
67
Issue
11
Pages
5408-5417
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-06-4095
OpenAlex
W2128414062
Cited by
301
References
40
FWCI
5.63
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species. https://app.cochat.ai/papers/10.1158/0008-5472.can-06-4095
The paper
De Milito, A., Iessi, E., Logozzi, M., Lozupone, F., Spada, M., Marino, M. L., Federici, C., Perdicchio, M., Matarrese, P., Lugini, L., Nilsson, A., & Fais, S. (2007). Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-4095

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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