Journal
INVESTIGATIONAL NEW DRUGS
Volume 27, Issue 2, Pages 111-119Publisher
SPRINGER
DOI: 10.1007/s10637-008-9141-4
Keywords
Aconitum alkaloid; C-20-diterpenoid alkaloids; Anticancer drugs; Radiation sensitization
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Funding
- Ministry of Education, Science and Culture of Japan [19659300, IK]
- Grants-in-Aid for Scientific Research [19659300] Funding Source: KAKEN
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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 gamma H2AX expression. The novel compounds derived from C-20-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C-19-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 gamma H2AX 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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