Apoptosis

, 11:2225

Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell sensitivity depends on catalase activity

  • Wei Wang
  • Masaaki Adachi
  • Rina Kawamura
  • Hiroki Sakamoto
  • Toshiaki Hayashi
  • Tadao Ishida
  • Kohzoh Imai
  • Yasuhisa Shinomura
Article

DOI: 10.1007/s10495-006-0287-2

Cite this article as:
Wang, W., Adachi, M., Kawamura, R. et al. Apoptosis (2006) 11: 2225. doi:10.1007/s10495-006-0287-2

Abstract

The sesquiterpene lactone, parthenolide (PTL), possesses strong anticancer activity against various cancer cells. We report that PTL strongly induced apoptosis in 4 multiple myeloma (MM) cell lines and primary MM cells (CD38+ high), but barely induced death in normal lymphocytes (CD38−/+low). PTL-mediated apoptosis correlated well with ROS generation and was almost completely inhibited by L-N-acetylcysteine (L-NAC), indicating the crucial role of oxidative stress in the mechanism. Among 4 MM cell lines, there is considerable difference in susceptibility to PTL. KMM-1 and MM1S cells sensitive to PTL possess less catalase activity than the less sensitive KMS-5 and NCI-H929 cells as well as normal lymphocytes. A catalase inhibitor 3-amino-1,2,4-triazole enhanced their PTL-mediated ROS generation and cell death. The siRNA-mediated knockdown of catalase in KMS-5 cells decreased its activity and sensitized them to PTL. Our findings indicate that PTL induced apoptosis in MM cells depends on increased ROS and intracellular catalase activity is a crucial determinant of their sensitivity to PTL.

Keywords

ROS Parthenolide Multiple myeloma Catalase NADPH oxidase 

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Wei Wang
    • 1
  • Masaaki Adachi
    • 1
    • 2
  • Rina Kawamura
    • 1
  • Hiroki Sakamoto
    • 1
  • Toshiaki Hayashi
    • 2
  • Tadao Ishida
    • 2
  • Kohzoh Imai
    • 2
  • Yasuhisa Shinomura
    • 2
  1. 1.Division of Molecular Oncology and Molecular Diagnosis, Graduate School of MedicineSapporo Medical University School of MedicineSapporoJapan
  2. 2.First Department of Internal MedicineSapporo Medical University School of MedicineSapporoJapan

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