A sesquiterpene lactone, costunolide, interacts with microtubule protein and inhibits the growth of MCF-7 cells

被引:55
作者
Bocca, C [1 ]
Gabriel, L [1 ]
Bozzo, F [1 ]
Miglietta, A [1 ]
机构
[1] Univ Turin, Dept Expt Med & Oncol, I-10125 Turin, Italy
关键词
costunolide; paclitaxel; microtubule protein; MCF-7; proliferation;
D O I
10.1016/j.cbi.2003.10.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Costunolide is an active sesquiterpene lactone of medicinal herbs with anti-inflammatory and potential anti-cancer activity. Nevertheless, the pharmacological pathways of costunolide have not yet been fully elucidated. In this study we showed that costunolide exerts a dose-dependent antiproliferative activity in the human breast cancer MCF-7 cells. In addition, light microscopy observations indicated that costunolide affected nuclear organization and reorganized microtubule architecture. The antiproliferative and antimicrotubular effects of costunolide were not influenced by paclitaxel, well-known microtubule-stabilizing anticancer agent. The microtubule-interacting activity of costunolide was confirmed by in vitro studies on purified microtubular protein. In fact, costunolide demonstrated polymerizing ability, by inducing the formation of well organized microtubule polymers. Our data suggest an interaction of costunolide with microtubules, which may represent a new intracellular target for this drug. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:79 / 86
页数:8
相关论文
共 24 条
[1]
Nuclear factor-kappa B and cancer: its role in prevention and therapy [J].
Bharti, AC ;
Aggarwal, BB .
BIOCHEMICAL PHARMACOLOGY, 2002, 64 (5-6) :883-888
[2]
ACTIVE COMPOUNDS FROM SAUSSUREA-LAPPA CLARKS THAT SUPPRESS HEPATITIS-B VIRUS SURFACE-ANTIGEN GENE-EXPRESSION IN HUMAN HEPATOMA-CELLS [J].
CHEN, HC ;
CHOU, CK ;
LEE, SD ;
WANG, JC ;
YEH, SF .
ANTIVIRAL RESEARCH, 1995, 27 (1-2) :99-109
[3]
Costunolide induces differentiation of human leukemia HL-60 cells [J].
Choi, JH ;
Seo, BR ;
Seo, SH ;
Lee, KT ;
Park, JH ;
Park, HJ ;
Choi, JW ;
Itoh, Y ;
Miyamoto, K .
ARCHIVES OF PHARMACAL RESEARCH, 2002, 25 (04) :480-484
[4]
Inhibition by costunolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1 [J].
Fukuda, K ;
Akao, S ;
Ohno, Y ;
Yamashita, K ;
Fujiwara, H .
CANCER LETTERS, 2001, 164 (01) :7-13
[5]
Giordano SH, 2002, CLIN CANCER RES, V8, P3360
[6]
Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity [J].
Gu, JQ ;
Gills, JJ ;
Park, EJ ;
Mata-Greenwood, E ;
Hawthorne, ME ;
Axelrod, F ;
Chavez, PI ;
Fong, HHS ;
Mehta, RG ;
Pezzuto, JM ;
Kinghorn, AD .
JOURNAL OF NATURAL PRODUCTS, 2002, 65 (04) :532-536
[7]
Hibasami H, 2003, INT J MOL MED, V12, P147
[8]
Costunolide, a sesquiterpene lactone from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway [J].
Jeong, SJ ;
Itokawa, T ;
Shibuya, M ;
Kuwano, M ;
Ono, M ;
Higuchi, R ;
Miyamoto, T .
CANCER LETTERS, 2002, 187 (1-2) :129-133
[9]
KAWAMORI T, 1995, CANCER RES, V55, P4053
[10]
Potentiation of 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone [J].
Kim, SH ;
Kang, SN ;
Kim, HJ ;
Kim, TS .
BIOCHEMICAL PHARMACOLOGY, 2002, 64 (08) :1233-1242