Antitumor Effects of Flavopiridol on Human Uterine Leiomyoma In Vitro and in a Xenograft Model

Authors
Hyun-Gyo LeeJong-Woo BaekSo-Jin ShinSang-Hoon KwonSoon-Do ChaWon-Jin ParkRosa ChungEun-Som ChoiGun-Ho LeeChi-Heum Cho
Department
Dept. of Obstetrics & Gynecology (산부인과학); Institute for Cancer Research (암연구소)
Issue Date
2014
Citation
Reproductive Sciences, Vol.21(9) : 1153-1160, 2014
ISSN
1933-7191
Abstract
Dysregulated cyclin-dependent kinases (CDKs) are considered a potential target for cancer therapy. Flavopiridol is a potent CDK inhibitor. In this study, the antiproliferative effect of the flavonoid compound flavopiridol and its mechanism in human uterine leiomyoma cells were investigated. The present study focused on the effect of flavopiridol in cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry was performed to determine the effect of flavopiridol on cell cycle. The expression of cell cycle regulatory-related proteins was evaluated by Western blotting. Cell viability and proliferation of uterine leiomyoma cells were significantly reduced by flavopiridol treatment in a dose-dependent manner. Flow cytometry results showed that flavopiridol induced G1 phase arrest. Flavopiridol-induced growth inhibition in uterine leiomyoma cells was associated with increased expression of p21cip/wafl and p27kip1 in a dose-dependent manner. Downregulation of CDK2/4 and Cyclin A with a concomitant increase in dephosphorylation of retinoblastoma was observed. This study demonstrates that flavopiridol inhibits cell proliferation by initiating G1 cell cycle arrest in human uterine leiomyoma.We also found that flavopiridol is effective in inhibiting xenografted human uterine leiomyoma growth. These results indicate that flavopiridol could prove to be a promising chemopreventive and therapeutic agent for human uterine leiomyoma.
Keywords
uterusleiomyomaflavopiridolp27kip1xenograft
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34334
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Cancer Research (암연구소)
Keimyung Author(s)
신소진; 권상훈; 차순도; 조치흠
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