Evodiamine inhibits 12-O-tetradecanoylphorbol-13-acetate-induced activator protein 1 transactivation and cell transformation in human hepatocytes.
Evodia rutaecarpa has been used to treat inflammatory digestive disorders in Asian countries. However, little is known about the antitumor activities of E. rutaecarpa and its bioactive constituent evodiamine (EVO). The aim of this study was to characterize the antitumor mechanisms of E. rutaecarpa and EVO in human hepatocytes. Human Chang liver cells were transfected with activator protein 1 (AP-1)-luciferase reporter gene and designated as Chang/AP-1 cells. The Chang/AP-1 cells were treated with E. rutaecarpa and its bioactive constituents, and challenged with the AP-1 stimulator 12-O-tetradecanoylphorbol-13- acetate (TPA). The present study showed that the methanol extract of E. rutaecarpa decreased the TPA-induced AP-1 transactivation in Chang/AP-1 cells, with an EC₅₀ value of 24.72 μg/mL. EVO inhibited the TPA-induced AP-1 transactivation and colony formation, with EC₅₀ values of 82 μM and 8.2 μM, respectively. Moreover, EVO significantly diminished the TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs). These results suggested that EVO treatment suppressed the TPA-induced AP-1 activity via the ERKs pathway. In conclusion, EVO inhibited the AP-1 activity and cellular transformation in human hepatocytes, suggesting that EVO was a potential agent for antitumor therapy.
Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
De-Cheng
DC
Chao
Li-Jen
LJ
Lin
Chien-Yun
CY
Hsiang
Chia-Cheng
CC
Li
Hsin-Yi
HY
Lo
Ji-An
JA
Liang
Shung-Te
ST
Kao
Shih-Lu
SL
Wu
Tin-Yun
TY
Ho
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D032086:Evodia / Q000737:chemistry; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011799:Quinazolines; D018808:Transcription Factor AP-1; C049639:evodiamine; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate