CONTEXT: Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. OBJECTIVE: To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. MATERIALS AND METHODS: In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. RESULTS: Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. DISCUSSION: These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. CONCLUSION: The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.
CONTEXT: Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. OBJECTIVE: To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. MATERIALS AND METHODS: In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCIDmice. RESULTS:Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. DISCUSSION: These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. CONCLUSION: The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.
Authors: Eduardo Chueca; Nadezda Apostolova; Juan V Esplugues; María A García-González; Ángel Lanas; Elena Piazuelo Journal: Front Pharmacol Date: 2016-11-25 Impact factor: 5.810
Authors: Kassidy A Hebert; Sergio Jaramillo; Wangjie Yu; Min Wang; Ratna Veeramachaneni; Vlad C Sandulache; Andrew G Sikora; Mark D Bonnen; Ananth V Annapragada; David Corry; Farrah Kheradmand; Raj K Pandita; Michelle S Ludwig; Tej K Pandita; Shixia Huang; Cristian Coarfa; Sandra L Grimm; Dimuthu Perera; George Miles; Yohannes T Ghebre Journal: Oncotarget Date: 2021-07-06