Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect

J Enzyme Inhib Med Chem. 2016 Aug;31(4):538-45. doi: 10.3109/14756366.2015.1046062. Epub 2015 May 28.

Abstract

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.

Keywords: Anti-acid drugs; lansoprazole; tumor acidity.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / classification*
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Drugs, Generic / chemical synthesis
  • Drugs, Generic / chemistry
  • Drugs, Generic / classification*
  • Drugs, Generic / pharmacology*
  • Female
  • Humans
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, SCID
  • Proton Pump Inhibitors / chemical synthesis
  • Proton Pump Inhibitors / chemistry
  • Proton Pump Inhibitors / classification*
  • Proton Pump Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Drugs, Generic
  • Proton Pump Inhibitors