Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo

Cho Hwa Liao, Shiow Lin Pan, Jih Hwa Guh, Ya Ling Chang, Hui Chen Pai, Chun Hung Lin, Che Ming Teng

研究成果: 雜誌貢獻文章同行評審

105 引文 斯高帕斯(Scopus)

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
頁(從 - 到)968-975
頁數8
期刊Carcinogenesis
26
發行號5
DOIs
出版狀態已發佈 - 2005
對外發佈Yes

ASJC Scopus subject areas

  • Cancer Research

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