This Article Full Text (PDF) All Versions of this Article: 1933719107312681v1 15/6/552    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Google Scholar Articles by Kim, D.-c. Articles by Cho, C.-H. PubMed PubMed Citation Social Bookmarking                   What's this?

Induction of Growth Inhibition and Apoptosis in Human Uterine Leiomyoma Cells by Isoliquiritigenin

Department of Oriental Medicine, Graduate School, Daegu Haany University, Kyungbuk, Korea

Sabarish Ramachandran, MS

Department of Obstetrics and Gynecology, Keimyung University

Seung-hee Baek, OMD

Department of Oriental Medicine, Graduate School, Daegu Haany University, Kyungbuk, Korea

Sang-Hoon Kwon, MD

Department of Obstetrics and Gynecology, Keimyung University

Kun-Young Kwon, MD

Department of Pathology School of Medicine, Keimyung University, Daegu, Korea

Soon-Do Cha, MD

Department of Obstetrics and Gynecology, Keimyung University

Insoo Bae, PhD

Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC

Chi-Heum Cho, MD

Department of Obstetrics and Gynecology, Keimyung University, chcho{at}kmu.ac.kr

Isoliquiritigenin(ISL), a calchone flavonoid, has cancer-preventing properties and is often used in Chinese medicine. In the present study, the authors use ISL to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry, annexin V apoptosis assay, and DNA fragmentation assay were performed to determine the effect of ISL on cell cycle and apoptosis. The expression of cell cycle regulatory—related proteins was evaluated by Western blot. The cell viability and proliferation of uterine leiomyoma cells were significantly reduced by ISL treatment in a dose-dependent manner. Flow cytometry results showed that ISL induced subG1 and G2/M arrest. DNA fragmentation assay and annexin V apoptosis assays revealed apoptosis induction. ISL-induced growth inhibition in uterine leiomyoma cells was associated with increased p21^Cip1/ Waf1 expression in a p53-dependent manner. Activation of caspase-3 and downregulation of Bcl-2, cdk 2/4, and E2F, with a concomitant increase in dephosphorylation of Rb and poly—ADP-ribose polymerase cleavage, were observed. This study demonstrates that ISL inhibits cell proliferation by initiating apoptosis in human uterine leiomyoma cells coupled with increased cell cycle arrest. These results indicate that ISL could prove to be a promising chemopreventive and therapeutic agent against human uterine leiomyoma.

Key Words: Isoliquiritigenin • human uterine leiomyoma • apoptosis.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?