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Apoptosis

, Volume 14, Issue 5, pp 655–664 | Cite as

Enhancement of radiation-induced apoptosis of human lymphoma U937 cells by sanazole

  • Da-Yong Yu
  • Qing-Li Zhao
  • Zheng-Li Wei
  • Takaharu Nomura
  • Ikuo Kashiwakura
  • Tsutomu V. Kagiya
  • Takashi Kondo
Original Paper

Abstract

Sanazole has been tested clinically as a hypoxic cell radiosensitizer. In this study, we determined whether sanazole enhances the radiation-induced apoptosis of human lymphoma U937 cells. Our results revealed that, compared with 10 mM sanazole or radiation alone, the combination of both resulted in a significant enhancement of apoptosis after 6 h, which was evaluated on the basis of DNA fragmentation, morphological changes, and phosphatidylserine externalization. Sanazole alone enhanced intracellular superoxide and hydrogen peroxide formation, which further increased when the cells were irradiated. Significant enhancement of Fas externalization, loss of mitochondrial membrane potential (MMP), and activation of caspase-3 and caspase-8 were observed after the combined treatment. Moreover, this combination could also enhance Bid activation, reduction of Hsp70 expression level and release of cytochrome c from the mitochondria to the cytosol. An immediate increase in the intracellular Ca2+ concentration ([Ca2+]i) was observed after the combined treatment. These results suggest that the intracellular superoxide and peroxide generated by sanazole might be involved in the enhancement of radiation-induced apoptosis, and that these effects are associated with modulation of the Fas-mitochondria-caspase-dependent pathway, an increase in [Ca2+]i, and a decrease in the Hsp70 expression levels.

Keywords

Sanazole Apoptosis Radiation Reactive oxygen species Calcium 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Da-Yong Yu
    • 1
  • Qing-Li Zhao
    • 1
  • Zheng-Li Wei
    • 1
  • Takaharu Nomura
    • 2
  • Ikuo Kashiwakura
    • 3
  • Tsutomu V. Kagiya
    • 4
  • Takashi Kondo
    • 1
  1. 1.Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  2. 2.Low Dose Radiation Research CenterCentral Research Institute of the Electric Power IndustryKomae201-8511Japan
  3. 3.Department of Radiological Life Sciences, Graduate School of Health SciencesHirosaki UniversityHirosakiJapan
  4. 4.Health Research FoundationKinki Invention CenterKyotoJapan

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