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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)968-975
Number of pages8
JournalCarcinogenesis
Volume26
Issue number5
DOIs
Publication statusPublished - 2005
Externally publishedYes

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Evodia
Breast Neoplasms
Pharmaceutical Preparations
Proto-Oncogene Proteins c-raf
Neoplasms
Tubulin
Heterografts
Polymerization
Phosphorylation
Paclitaxel
In Vitro Techniques
evodiamine
Drug Resistance
Nude Mice
Doxorubicin
Cell Cycle
Apoptosis

ASJC Scopus subject areas

  • Cancer Research

Cite this

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

In: Carcinogenesis, Vol. 26, No. 5, 2005, p. 968-975.

Research output: Contribution to journalArticle

Liao, Cho Hwa ; Pan, Shiow Lin ; Guh, Jih Hwa ; Chang, Ya Ling ; Pai, Hui Chen ; Lin, Chun Hung ; Teng, Che Ming. / 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. In: Carcinogenesis. 2005 ; Vol. 26, No. 5. pp. 968-975.
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