The effect of two dietary and a synthetic phytoestrogen on transepithelial calcium transport in human intestinal-like Caco-2 cells

Summary

Background

Recently, dietary phytoestrogens (PEs) have been suggested as possible alternatives to estrogen therapy, as a means of preventing bone loss associated with ovarian hormone deficiency. PEs are non-steroidal, plant-derived compounds that exhibit some estrogen-like activity in some tissues, and which appear to prevent postmenopausal bone loss. While PEs act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption.

Aim of the study

Therefore, the aim of this study was to investigate the effect of two dietary PEs (coumestrol and apigenin) as well as a synthetic PE, ipriflavone, on Ca absorption in human Caco-2 intestinal-like cells.

Methods

Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On d 21, the Caco-2 monolayers (n 10–16 per treatment), grown in estrogen-free or low-estrogen media, were then exposed to 10 nM-1,25 (OH)₂ D₃, or 50 µM ipriflavone, -coumestrol or -apigenin for 48 hours. After exposure, transepithelial and transcellular transport of ⁴⁵Ca and fluorescein transport (a marker of paracellular diffusion) were measured.

Results

As expected, 1,25 (OH)₂ D₃ stimulated Ca absorption. Treatment with coumestrol or apigenin had no effect on Ca transport. On the other hand, ipriflavone increased total Ca transport (by about 1.5-fold, P < 0.05) under lowestrogen conditions, but not under estrogen-free conditions. This increase in total Ca transport by ipriflavone was via an increased transcellular Ca transport (by about 2-fold, P < 0.05) relative to control.

Conclusion

In conclusion, the protective effect of dietary PE on bone mass would appear to be due to their direct effect(s) on bone cells, as opposed to an indirect effect on bone by stimulation of intestinal Ca absorption.