Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth.
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 gammaH2AX 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 gammaH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.
Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, 036-8564, Japan.
Masaharu
M
Hazawa
Koji
K
Wada
Kenji
K
Takahashi
Takao
T
Mori
Norio
N
Kawahara
Ikuo
I
Kashiwakura
D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000302:isolation & purification / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D028321:Plant Preparations / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D018517:Plant Roots; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; C468783:H2AX protein, human; D006657:Histones; D028321:Plant Preparations; D011838:Radiation-Sensitizing Agents