Acidic environments enhance the inhibitory effect of statins on proliferation of synovial cells.

Abstract

Many previous studies in animal models and clinical investigations have suggested that statins are useful chemotherapeutics against rheumatoid arthritis, whereas in vitro experiments using synovial cell lines showed no significant effect of statins on cell proliferation until now. Since synovial fluid in rheumatoid joint knee was found to be acidic, we examined the effect of statins on human synovial sarcoma cell line SW982 cells in acidic medium. Statins suppressed the proliferation of SW982 cells at pH6.7, while the suppression was very weak in pH7.5 medium. It was shown that the suppression was caused by the decrease in geranylgeranyl diphosphate, suggesting that a geranylgeranylated protein(s) has an essential role in cell proliferation of SW982 cells under acidic conditions. Our present data clearly implied that statins had high efficacy against SW982 cells in acidic medium whose pH is close to that of rheumatoid arthritis loci in patients. These results lead us to anticipate that screening of chemicals having high therapeutic efficacy in acidic medium promotes the development of new microenvironment-dependent medicines for chemotherapies against rheumatoid arthritis.

• Authors: Toshihiko Fukamachi, Xin Wang, Yusuke Mochizuki, Chie Maruyama, Hiromi Saito, Hiroshi Kobayashi
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 17 Issue 1 Pg. 148-53 (Sep 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 23769886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Ionophores
• Enzyme Inhibitors
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Ionomycin
• Lovastatin
• Cantharidin

Topics

• Calcium Ionophores (pharmacology)
• Cantharidin (pharmacology)
• Cell Line, Tumor
• Cell Proliferation
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects, physiology)
• Humans
• Hydrogen-Ion Concentration
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Ionomycin (pharmacology)
• Lovastatin (pharmacology)
• Sarcoma, Synovial (metabolism)
• Synovial Membrane (cytology)