Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid

Paracellular permeability (PCP) is governed by tight junctions (TJs) in epithelial cells, acting as cell-cell adhesion structures, the aberration of which is known to be linked to the dissociation and metastasis of breast cancer cells. This study hypothesized that the function of TJs in human breast cancer cells can be augmented by gamma linolenic acid (GLA), selenium (Se), and iodine (I) in the presence of 17-beta-estradiol, as these molecules are known to increase TJ functions in endothelial cells, using assays of trans-epithelial resistance (TER), PCP, immunofluorescence, and in vitro invasion and motility models. GLA, I, and Se individually increased TER of MDA-MB-231 and MCF-7 human breast cancer cells. The combination of all three agents also had a significant increase in TER. Addition of GLA/Se/I reduced PCP of both breast cancer cell lines. GLA/Se/I reversed the effect of 17-beta-estradiol (reduced TER, increased PCP). Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h, there was increasing relocation to breast cancer cell-cell junctions of occludin and ZO-1 in MCF-7 cells. Moreover, treatment with GLA/Se/I, alone or in combination, significantly reduced in vitro invasion of MDA-MB-231 cells through an endothelial cell barrier (P < 0.0001) and reduced 17-beta-estradiol induced breast cancer cell motility (P < 0.0001). Our previous work has demonstrated that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells; this has now proved to be true of human breast cancer cells. This combination also completely reversed the effect of 17-beta-estradiol in these cells.