Indole-3-carbinol and genistein inhibit growth of human uterine leiomyoma cells

Jeong, Hee Woong; Kim, Yun Ok; Shin, So Jin; Kwon, Sang Hoon; Cha, Soon Do; Cho, Chi Heum

Abstract

OBJECTIVE
To determine whether Indole-3-carbinol (I3C) can enhance the inhibitory effect of genistein on a human uterine leiomyoma cells.
METHODS
Five uterine leiomyoma tissues were obtained from hysterectomies conducted on the benign diseases and cultured primarily. MTS reduction assay was carried out to determine the viability of human uterine leiomyoma cells. Cell cycle analysis for I3C and genistein treated human uterine leiomyoma cells was done by Fluorescent activated cell sorter (FACS) analysis. To detect the presence and expression of cell cycle related proteins was done by Western blot analysis.
RESULTS
I3C and genistein induced growth inhibition in a dose dependent manner, treatment with 100 micro mol/L I3C and 100 micro mol/L genisten blocked 60% cell growth. FACS results showed that treatment with the I3C and genistein increased the percentage of cells in G2/M phase and decreased S phase. From Western blot analysis it revealed I3C and genistein induced the expression of p53, p21, and p27 increasing. Reduced expression of cyclin B1 and cyclin E were detected in treatment with I3C and genistein. The expression levels of these proteins correlate with G2/M cell cycle arrest. Activation of caspase pathway and fragmentation of PARP did not take place.
CONCLUSIONS
These results demonstrate that I3C enhances genistein-mediated uterine leiomyoma cell growth inhibition through the cell cycle arrest at G2/M phase by decreasing the production of cyclin B1. Because of the synergistic effect of I3C and genistein, the potential exists for the therapeutic efficacy of each phytochemical when used in combination.