Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties
| Autor: | Li-He Zhang, Michèle Garès, Ji-Mei Min, Michel Wright, Min Li, Jing-Rong Ciu, Kui Wang, Jean Cros, Ying Ye, Jeanne Leung-Tack |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Time Factors Mitosis Antineoplastic Agents HL-60 Cells Biology Microtubules Inhibitory Concentration 50 Mice chemistry.chemical_compound Tubulin In vivo Microtubule Tumor Cells Cultured Animals Humans Protein Isoforms Ajoene Disulfides Enzyme Inhibitors Fluorescent Antibody Technique Indirect Garlic Cytoskeleton Dose-Response Relationship Drug Plant Extracts Cell growth General Medicine Cell cycle Flow Cytometry Molecular biology In vitro Biochemistry chemistry Cell culture Sulfoxides Cell Division Protein Binding |
| Zdroj: | Carcinogenesis. 23:573-579 |
| ISSN: | 1460-2180 |
| DOI: | 10.1093/carcin/23.4.573 |
| Popis: | Ajoene, a garlic stable oil-soluble sulfur rich compound was generally isolated as a mixture of two isomers [(E, Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide]. It has been described essentially as a potent inhibitor of platelet aggregation in vitro and in vivo. The antiproliferative effects of ajoene and experiments using a single isomer had received little attention. The present study aims at defining the antitumor activities of cis-Z-ajoene in vitro and in vivo. Antiproliferative activity of Z-ajoene was demonstrated against a panel of human tumor cell lines with IC(50) values varying from 5.2 mM to 26.1 mM and at a lower extent in normal marsupial kidney cells (PtK2). Meanwhile, Z-ajoene arrested HL60 cells in G(2)/M phase of cell cycle in a dose and time-dependent way. In PtK2 cells, exposure to 20 microM Z-ajoene for 6 h induced a complete disassembly of the microtubule network, that was associated with an increased number of cells blocked in early mitotic stages. An IC(50) for microtubule disassembly of 1 microM was determined by a fully automated microplate-based multi-detection reader. In vitro, a reversible inhibition of the microtubule protein assembly was observed with an IC(50) of 25 microM Z-ajoene. In vivo, Z-ajoene inhibited tumor growth by 38% and 42% in mice grafted with sarcoma 180 and hepatocarcinoma 22, respectively. For the first time, Z-ajoene was shown to be a potent inhibitor of tumor cell growth both in vitro and in vivo. The microtubule cytoskeleton appeared to be one of the Z-ajoene targets, but the mechanisms by which Z-ajoene interacted with microtubule appeared different from those of other microtubule poisons such as those of the Vinca alkaloids family. The ability of Z-ajoene to preferentially suppress the growth of neoplastic cells could provide a new approach in tumor therapy. |
| Databáze: | OpenAIRE |
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