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

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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.

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Authors and Affiliations

  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

    Wei Wang, Masaaki Adachi, Rina Kawamura & Hiroki Sakamoto

  2. First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

    Masaaki Adachi, Toshiaki Hayashi, Tadao Ishida, Kohzoh Imai & Yasuhisa Shinomura

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  1. Wei Wang
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  2. Masaaki Adachi
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  3. Rina Kawamura
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  4. Hiroki Sakamoto
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  5. Toshiaki Hayashi
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  8. Yasuhisa Shinomura
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Correspondence to Masaaki Adachi.

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Wang, W., Adachi, M., Kawamura, R. et al. Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell sensitivity depends on catalase activity. Apoptosis 11, 2225–2235 (2006). https://doi.org/10.1007/s10495-006-0287-2

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  • DOI: https://doi.org/10.1007/s10495-006-0287-2

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