Liao C.-H.Pan S.-L.JIH-HWA GUHChang Y.-L.Pai H.-C.Lin C.-H.Teng C.-M.2021-06-022021-06-0220051433334https://www.scopus.com/inward/record.uri?eid=2-s2.0-19844377252&doi=10.1093%2fcarcin%2fbgi041&partnerID=40&md5=e34343644906896651bb0a988c7be674https://scholars.lib.ntu.edu.tw/handle/123456789/564857Drug 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]SDG3evodiamine; 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; Quinolinesjournal article10.1093/carcin/bgi041157056002-s2.0-19844377252