title: Antitumor effects of flavopiridol on human uterine leiomyoma in vitro and in a xenograft model.
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 p21(cip/wafl) and p27(kip1) 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.
authors.affiliation: Institute for Cancer Research, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hyun-Gyo
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Cha Gumi Medical Center, Cha University, Gyeongsangbukdo, Republic of Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Baek
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Soon-Do
authors.initials: SD
authors.lastname: Cha
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Institute for Cancer Research, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Rosa
authors.initials: R
authors.lastname: Chung
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Eun-Som
authors.initials: ES
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, Cha Gumi Medical Center, Cha University, Gyeongsangbukdo, Republic of Korea.
authors.forename: Gun-Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Institute for Cancer Research, Keimyung University School of Medicine, Daegu, Republic of Korea Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea chcho@kmu.ac.kr.
authors.forename: Chi-Heum
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib
keywords: flavopiridol; leiomyoma; p27kip1; uterus; xenograft