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Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

Abstract
Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies.
AuthorsAndrea Canitano, Elisabetta Iessi, Enrico Pierluigi Spugnini, Cristina Federici, Stefano Fais
JournalCancer letters (Cancer Lett) Vol. 376 Issue 2 Pg. 278-83 (Jul 01 2016) ISSN: 1872-7980 [Electronic] Ireland
PMID27084522 (Publication Type: Journal Article)
CopyrightCopyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Proton Pump Inhibitors
  • Lansoprazole
  • Caspases
  • Omeprazole
Topics
  • Apoptosis (drug effects)
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Dose-Response Relationship, Drug
  • Humans
  • Lansoprazole (pharmacology)
  • Multiple Myeloma (drug therapy, enzymology, pathology)
  • Omeprazole (pharmacology)
  • Proton Pump Inhibitors (pharmacology)
  • Signal Transduction (drug effects)
  • Time Factors

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