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
Journal
Carcinogenesis
Journal Volume
26
Journal Issue
5
Pages
968-975
Date Issued
2005
Author(s)
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. ? Oxford University Press 2005; all rights reserved.
SDGs
Other Subjects
evodiamine; paclitaxel; protein bcl 2; Raf protein; tubulin; alkaloid; antineoplastic agent; Evodia fruit; evodiamine; Gosyuyu; paclitaxel; plant extract; protein bcl 2; quinazoline derivative; quinoline derivative; Raf protein; animal experiment; animal model; antineoplastic activity; apoptosis; article; breast cancer; cell cycle; cell cycle G2 phase; cell proliferation; concentration response; controlled study; female; flow cytometry; fluorescence activated cell sorting; human; human cell; immunocytochemistry; in vitro study; in vivo study; microtubule assembly; mouse; multidrug resistance; nonhuman; priority journal; protein phosphorylation; tumor xenograft; animal; breast tumor; drug effect; drug resistance; metabolism; microtubule; nude mouse; phosphorylation; physiology; Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Proliferation; Drug Resistance, Neoplasm; Evodia; Female; Humans; Mice; Mice, Nude; Microtubules; Paclitaxel; Phosphorylation; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-raf; Quinazolines; Quinolines
Type
journal article