Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth
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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 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.
KeywordsAconitum alkaloid C20-diterpenoid alkaloids Anticancer drugs Radiation sensitization
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).
- 4.Zhang M, Boyer M, Rivory L et al (2004) Radiosensitization of vinorelbine and gemcitabine in NCL-H460 non-small-cell lung cancer cells. Int J Radiat Oncol Biol Phys 58:33–60Google Scholar
- 13.Negulyaev Yu A, Vedernikova EA, Savokhina GA (1990) Aconitine-induced modification of signal sodium channels in neuroblastoma cell membrane. Gen Physiol Biophys Commun 9:167–176Google Scholar
- 18.Wada K, Bando H, Amiya T (1985) Two new C20-diterpenoid alkaloids from Aconitum yesoense var. macroyesoense (NAKAI) TAMURA, structures of dehydrolucidusculine and N-deethyldehydrolucidusculine. Heterocycles 23:2473–2477Google Scholar
- 19.Bando H, Wada K, Amiya T et al (1987) Studies on Aconitum species V. Constituents of Aconitum yesoense var. macroyesoense (NAKAI) TAMURA. Heterocycles 26:2623–2637Google Scholar
- 20.Wada K, Bando H, Amiya T (1988) Studies on Aconitum species VI. Yesoline, a new C20-diterpenoid alkaloid from Aconitum yesoense var. macroyesoense (NAKAI) TAMURA. Heterocycles 27:1249–1252Google Scholar
- 22.Wada K, Bando H, Kawahara N (1990) Studies on Aconitum species. XIII. Two new diterpenoid alkaloids from Aconitum yesoense var. macroyesoense (NAKAI) TAMURA VI. Heterocycles 31:1081–1088Google Scholar
- 23.Bando H, Kanaiwa Y, Wada K et al (1981) Structure of deoxyjesaconitine. A new diterpene alkaloid from Aconitum subcuneatum NAKAI. Heterocycles 16:1723–1725Google Scholar
- 24.Mori T, Bando H, Kanaiwa Y et al (1983) Studies on the constituents of Aconitum Species. II. Structure of deoxyjesaconitine. Chem Pharm Bull 31:2884–2886Google Scholar
- 25.Wada K, Bando H, Mori T et al (1985) Studies on the constituents of Aconitum Species. III. On the components of Aconitum subcuneatum NAKAI. Chem Pharm Bull 33:3658–3661Google Scholar
- 26.Wada K, Bando H, Watanabe M et al (1985) Studies on the constituents of Aconitum Species. IV. On the components of Aconitum japonicum THUNB. Chem Pharm Bull 33:4717–4722Google Scholar
- 32.Hall EJ (2000) Radiobiology for the radiologist. Lippincott, PhiladelphiaGoogle Scholar