Generation of reactive oxygen species is required for bucillamine, a novel anti-rheumatic drug, to induce apoptosis in concert with copper

  • Sawada T
  • Hashimoto S
  • Furukawa H
 et al. 
  • 6

    Readers

    Mendeley users who have this article in their library.
  • 13

    Citations

    Citations of this article.

Abstract

Rheumatoid arthritis (RA) is considered to be a proliferative disorder of synovial tissue, which is composed of macrophage-like, fibroblast-like and dendritic cells. Bucillamine (BUC) is a novel disease-modifying anti-rheumatic drug, which is a structural analogue of cysteine. Some of the pharmacological actions of BUC have been shown to depend on the generation of reactive oxygen species (ROS) in the presence of copper. In this study, we examined whether BUC in concert with copper can induce apoptosis via generation of ROS. THP.1, a human monocytic cell line, was used as surrogate for synovial cells. We observed that BUC plus copper can induce THP.1 to undergo apoptosis. as evidenced by the presence of DNA degradation, which is preceded by ROS generation and increase in membrane permeability. Moreover, catalase rescued THP.1 from BUC-mediated cell death, indicating that generation of ROS is essential for the induction of apoptosis. Red blood cells (RBC), probably acting as a scavenger of ROS, also rescued THP.1 from cell death mediated by BUC plus copper. Collectively, we suggest that ROS derived from BUC in the presence of copper may suppress the outgrowth of rheumatoid arthritis synovial cells in vivo through the induction of apoptosis.

Author-supplied keywords

  • apoptosis
  • bucillamine
  • reactive oxygen species

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Tetsuji Sawada

  • Shiori Hashimoto

  • Hiroshi Furukawa

  • Shigeto Tohma

  • Tetsufumi Inoue

  • Koji Ito

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free