摘要
Drug resistance is one of the main obstacles to the successful treatment of cancer. The availability of agents that are highly effective against drug-resistant cancer cells is therefore essential. The present study was performed to examine the anticancer effects of evodiamine, a major constituent of the Chinese herb Evodiae fructus, in adriamycin-resistant human breast cancer NCI/ADR-RES cells. Evodiamine inhibited the proliferation of NCI/ ADR-RES cells in a concentration-dependent manner with a GI50 of 0.59 ± 0.11 μM. This agent also caused a substantial apoptosis at 1 μM. FACScan flow cytometric analysis of cell cycle progression revealed that a G 2/M arrest was initiated after a 12-h exposure to the drug. Evodiamine increased tubulin polymerization as determined by the immunocytochemical and in vivo tubulin polymerization analyses. In a time- and concentration-dependent manner, evodiamine also promoted the phosphorylations of Raf-1 kinase and Bcl-2. The phosphorylation site of Raf-1 kinase was identified to be serine338. The in vivo anticancer effects of evodiamine were evaluated in Balb-c/nude mice following a tumor xenograft implantation of NCI/ADR-RES cells. The antitumor activity of evodiamine against the human multiple-drug resistant tumor xenograft was found to be superior to that of paclitaxel. Evodiamine therefore represents a highly promising chemotherapeutic agent in the treatment of human multiple-drug resistant cancer cells.
原文 | 英語 |
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頁(從 - 到) | 968-975 |
頁數 | 8 |
期刊 | Carcinogenesis |
卷 | 26 |
發行號 | 5 |
DOIs | |
出版狀態 | 已發佈 - 2005 |
ASJC Scopus subject areas
- 癌症研究