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

Abstract

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.

Treating gynaecological disorders with traditional Chinese medicine: a review

“…Isoliquiritigenin (ISL), a calchone flavonoid, has cancer-preventing properties and is often used in TCM. ISL has been found to inhibit cell proliferation by initiating apoptosis in human uterine leiomyoma cells coupled with the increased cell cycle arrest, indicating that ISL could prove to be a promising chemo-preventive and therapeutic agent against human uterine leiomyoma ( Kim et al, 2008).…”

Isoliquiritigenin inhibits colorectal cancer cells HCT-116 growth by suppressing the PI3K/AKT pathway

“…In our study, ISL treatment inhibited Akt and mTOR activation through reduction of p-AKT and p-mTOR without changes in total Akt and mTOR expression. Furthermore, our results apoptosis [28]. Bax, Bcl-2, and Caspase proteins are the key molecular players that regulate cellular apoptosis [29,30].…”

Dietary chalcones with chemopreventive and chemotherapeutic potential

“…In addition, phosphorylation of cell division cycle (Cdc)2 was enhanced concurrent with reduction of Cdc25c levels, leading to inactivation of Cdc2-cyclin B1 complexes and subsequent late G2/M phase arrest [97]. Similarly, perturbation of the cell cycle at the G2/M phase by induction of universal inhibitors of Cdks, such as p21 (CIP1/WAF1) and p27, was observed in leukemia CCRF-CEM cells [195], human cervical cancer HeLa cells [139], uterine leiomyoma cells [68] lung cancer A549 cells [59], and human prostate cancer LNCaP cells [65]. Licochalcone A (18) led to G2/M arrest by similar mechanisms via induction of p21 and p27, attenuation of Cdks 2, 4, and 6, and downregulation of cyclin D1 in androgen-independent PC-3 prostate cancer cells [38,188].…”

“…Isoliquiritigenin (2) has also been shown to significantly reduce viability and proliferation in a dose-dependent manner in uterine leiomyoma cells, human lung cancer cells, and CCRF-CEM leukemia cells. These effects were related to induction of apoptosis and increased cell cycle arrest [59, 68,195]. Interestingly, isoliquiritigenin (2) downregulates proliferation in HL-60 cells and mediates their monocytic differentiation [100].…”