Buthionine Sulfoximine and 1,25-Dihydroxyvitamin D Induce Apoptosis in Breast Cancer Cells via Induction of Reactive Oxygen Species

Abstract

Calcitriol or 1,25(OH)2D3 is a negative growth regulator of breast cancer cells. The aim of this study was to determine whether L-buthionine-S,R-sulfoximine, a glutathione-depleting drug, modifies the antiproliferative effects of 1,25(OH)2D3 on MCF-7 cells . For comparison, we included studies in MCF-7 cells selected for vitamin D resistance and in human mammary epithelial cells transformed with SV40 and ras. Our data indicate that L-buthionine-S,R-sulfoximine enhances the growth inhibition of 1,25(OH)2D3 in all transformed breast cell lines. This effect is mediated by ROS leading to apoptosis. In conclusion, BSO alters redox state and sensitizes breast cancer cells to calcitriol mediated apoptosis.