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Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth

  • Masaharu Hazawa
  • Koji Wada
  • Kenji Takahashi
  • Takao Mori
  • Norio Kawahara
  • Ikuo KashiwakuraEmail author
PRECLINICAL STUDIES

Summary

Little information has so far been reported regarding the antiproliferative properties of Aconitum alkaloids against human tumor cells despite of their intense toxicities. In the present study, the antitumor properties and radiation sensitizing effects were investigated by various types of novel derivatives prepared from Aconitum alkaloids. The antitumor properties were investigated against human tumor cell lines, A172, A549, HeLa and Raji, respectively, by a cell growth, a clonogenic assay, cell cycle distribution, cell cycle related molecules and γH2AX expression. The novel compounds derived from C20-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C19-norditerpenoid alkaloids and their derivatives showed either no effect or only a slight effect. One of the compounds also showed radiosensitizing properties on A549 cells. These effects are not related to either the cell cycle distribution, the enhancement of apoptosis or the γH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.

Keywords

Aconitum alkaloid C20-diterpenoid alkaloids Anticancer drugs Radiation sensitization 

Notes

Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research Fund from the Ministry of Education, Science and Culture of Japan (No. 19659300, IK).

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Masaharu Hazawa
    • 1
  • Koji Wada
    • 2
  • Kenji Takahashi
    • 1
  • Takao Mori
    • 3
  • Norio Kawahara
    • 3
  • Ikuo Kashiwakura
    • 1
    Email author
  1. 1.Department of Radiological Life SciencesHirosaki University Graduate School of Health SciencesHirosakiJapan
  2. 2.School of PharmacyHokkaido Pharmaceutical UniversityOtaruJapan
  3. 3.Research CenterNorth Japan Chemical Inc.EniwaJapan

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