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Apoptosis. 2006 Dec;11(12):2225-35.

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

Author information

1
Division of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan.

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.

PMID:
17051330
DOI:
10.1007/s10495-006-0287-2
[Indexed for MEDLINE]

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