Induction of growth inhibition and apoptosis in human uterine leiomyoma cells by isoliquiritigenin.
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.
Kim
Dong-chul
DC
Department of Oriental Medicine, Graduate School, Daegu Haany University, Kyungbuk, Korea.
Ramachandran
Sabarish
S
Baek
Seung-hee
SH
Kwon
Sang-Hoon
SH
Kwon
Kun-Young
KY
Cha
Soon-Do
SD
Bae
Insoo
I
Cho
Chi-Heum
CH
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D047188:Chalcones; C040920:isoliquiritigenin