Effectiveness of KBU2046, Calcitriol, Dienogest and N-Butyrate or Their Combinations on Immortalized Endometriotic Epithelial Cells.

Endometriosis is a chronic disease that causes endometrial tissues to migrate and grow outside the uterus and is often associated with pain and infertility. The growths are estrogen-dependent but progesterone-resistant due to the lack of progesterone receptors. In the U.S., estrogen deprivation is the primary approach to treating the disease, which often leads to severe consequences such as osteoporosis and menopausal symptoms. KBU2046 is a chemical analog of genistein that has been shown to effectively inhibit the motility of prostate cancer cells with no toxicity to normal cells or estrogenic activity (Li Xu et al., 2010). This in vitro study showed that KBU2046 at 10μM significantly decreased the viability of 12Z cells to 27% and 34% at 24 hours and 48 hours posttreatment, respectively. At 48 hours post-treatment, micromolar concentrations of the combinations of KBU2046 with dienogest or calcitriol effectively decreased the viability of 12Z cells to 16% and 58.9%, respectively. KBU2046 with sodium butyrate decreased viability to 7.7%, but millimolar concentrations of the latter were required. KBU2046, in combination with calcitriol, synergistically decreased the migration and colony formation of the 12Z cells to 19.3% and 45.7%, respectively. KBU2046 and Calcitriol-treated 12Z cells are slower to the recovery of growth following treatment. KBU2046 and calcitriol decreased the secretion of PGE2 to 6.5% and 16.7%, respectively, while ethanol and the combinations of ethanol and DMSO increased the secretion of PGE2 to 83.8%, and 63.2%, respectively. In conclusion, a combination of KBU2046 and calcitriol at micromolar concentrations markedly inhibited the migration and growth of endometrial cells while decreasing the secretion of a key inflammatory molecule. In vivo studies with mouse models are needed to evaluate using a combination of KBU2046 and calcitriol for endometriosis therapy and whether millimolar plasma concentrations can be safely achieved by dietary means.