Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration
Mariko Miyazawa, Masanori Yasuda, Masaki Miyazawa, Naoki Ogane, Tomomi Katoh, Mitsutake Yano, Takeshi Hirasawa, Mikio Mikami, Hitoshi Ishimoto
Abstract
BACKGROUND/AIM: Advanced ovarian clear-cell carcinoma (CCC) fails to respond to standard chemotherapy, and has a poor prognosis. Since hypoxia-inducible factor-1 (HIF-1) stimulates various genes involved in cancer, we aimed to examine the efficacy of silibinin, an active component of milk thistle belonging to Asteraceae, in suppressing HIF-1 activity, and elucidate the underlying mechanism in human CCC cell lines. MATERIALS AND METHODS: Human ovarian CCC cell lines HAC-2, OVISE, and RMG-1 were treated with 500 μM silibinin for 4 h under normoxic and hypoxic conditions. Using DNA microarray, we analysed genes whose expression modulated more than 2-fold in response to hypoxia, whereas HIF-1α expression was measured using ELISA. RESULTS: Silibinin treatment decreased HIF-1α protein in all cell lines, and eIF4E2 and RPS6 mRNA in HAC-2 and RMG-1 cells. CONCLUSION: Silibinin suppressed HIF-1α protein under hypoxic conditions in CCC cell lines and could be a potential anti-cancer drug.