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

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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.

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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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Authors and Affiliations

  1. Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, 036-8564, Japan

    Masaharu Hazawa, Kenji Takahashi & Ikuo Kashiwakura

  2. School of Pharmacy, Hokkaido Pharmaceutical University, 7-1, Katsuraoka-cho, Otaru, 047-0264, Japan

    Koji Wada

  3. Research Center, North Japan Chemical Inc., Eniwa RBP 308, 1-1, 3-Meguminokita, Eniwa, 061-1374, Japan

    Takao Mori & Norio Kawahara

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  1. Masaharu Hazawa
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  2. Koji Wada
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  4. Takao Mori
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Correspondence to Ikuo Kashiwakura.

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Hazawa, M., Wada, K., Takahashi, K. et al. Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth. Invest New Drugs 27, 111–119 (2009). https://doi.org/10.1007/s10637-008-9141-4

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  • DOI: https://doi.org/10.1007/s10637-008-9141-4

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