title: 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.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Canitano
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iessi
authors.affiliation: SAFU, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Enrico Pierluigi
authors.initials: EP
authors.lastname: Spugnini
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Federici
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: stefano.fais@iss.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D064747:Lansoprazole / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D020169:Caspases; D009853:Omeprazole
keywords: Apoptosis; Cancer; Hematological malignancy; Lanzoprazole; Omeprazole