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

被引：86

作者：

Hazawa, Masaharu ^{[1
]}

Wada, Koji ^{[2
]}

Takahashi, Kenji ^{[1
]}

Mori, Takao ^{[3
]}

Kawahara, Norio ^{[3
]}

Kashiwakura, Ikuo ^{[1
]}

机构：

[1] Hirosaki Univ, Dept Radiol Life Sci, Grad Sch Hlth Sci, Hirosaki, Aomori 0368564, Japan

[2] Hokkaido Pharmaceut Univ, Sch Pharm, Otaru, Hokkaido 0470264, Japan

[3] N Japan Chem Inc, Res Ctr, Eniwa 0611374, Japan

来源：

INVESTIGATIONAL NEW DRUGS | 2009年 / 27卷 / 02期

关键词：

Aconitum alkaloid; C-20-diterpenoid alkaloids; Anticancer drugs; Radiation sensitization; CUTANEOUS BLOOD-FLOW; MACROYESOENSE NAKAI TAMURA; DITERPENOID ALKALOIDS; PSEUDOKOBUSINE DERIVATIVES; CONSTITUENTS; RADIATION; APOPTOSIS; DNA; GEMCITABINE; GAMMA-H2AX;

D O I：

10.1007/s10637-008-9141-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：111 / 119

页数：9

共 35 条

[1]

2 NEW DITERPENOID ALKALOIDS FROM DELPHINIUM-PACIFIC-GIANT AND REVISED C-13-NMR ASSIGNMENT OF DELPHELINE [J].

BANDO, H ;

WADA, K ;

TANAKA, J ;

KIMURA, S ;

HASEGAWA, E ;

AMIYA, T .

HETEROCYCLES, 1989, 29 (07) :1293-1300

[2]

BANDO H, 1985, CHEM PHARM BULL, V33, P4717

[3]

BANDO H, 1981, HETEROCYCLES, V16, P1723

[4]

BANDO H, 1987, HETEROCYCLES, V26, P2623

[5]

BANDO H, 1988, HETEROCYCLES, V27, P2167

[6]

Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results [J].

Baumann, M ;

Krause, M .

RADIOTHERAPY AND ONCOLOGY, 2004, 72 (03) :257-266

[7]

CHAN TYK, 1994, VET HUM TOXICOL, V36, P326

[8]

8-O-Azeloyl-14-benzoylaconine:: A new alkaloid from the roots of Aconitum karacolicum Rapcs and its antiproliferative activities [J].

Chodoeva, A ;

Bosc, JJ ;

Guillon, J ;

Decendit, A ;

Petraud, M ;

Absalon, C ;

Vitry, C ;

Jarry, C ;

Robert, J .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (23) :6493-6501

[9]

Radiation could induce p53-independent and cell cycle - unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells [J].

Didelot, C ;

Mirjolet, JF ;

Barberi-Heyob, M ;

Ramacci, C ;

Merlin, JL .

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2002, 80 (07) :638-643

[10]

FELDKAMP A, 1991, MONATSSCHR KINDERH, V139, P366

← 1 2 3 4 →