Cell Cycle Arrest and Apoptosis Responses of Human Breast Epithelial Cells to the Synthetic Organosulfur Compound p-Methoxyphenyl p-Toluenesulfonate

Abstract

Background: There are several studies documenting that organosulfur compounds show promise as anticancer agents. Although some mechanisms of the antiproliferative activity of naturally occurring organosulfur compounds have been elucidated, few studies have reported the differential response of human breast cells to these compounds. Materials and Methods: The effect of the synthetic sulfonate ester, p-methoxyphenyl p-toluenesulfonate on growth inhibitory activity depending upon the estrogen-receptor (ER), p53, bcl-2 and caspase-3 status of cells was investigated by comparing its effects on three distinct human breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-453) and on one normal human mammary epithelial cell line (MCF-10A). Results: This sulfonate ester selectively killed cancer cells at doses of 100 μM. Flow cytometry analysis showed that treatment with p-methoxyphenyl p-toluenesulfonate caused different cell cycle responses in the four cell lines but no clear association with p53 status was observed. Apoptosis was also induced in cells harboring different levels of Bcl-2 expression, but again independently of the p53 or ER status of the cells. Conclusion: These results suggest that p-methoxyphenyl p-toluenesulfonate acts on multiple signaling pathways leading to growth inhibition and activation of mechanisms of cell death selectively affecting survival of breast cancer cells. Thus, p-methoxyphenyl p-toluenesulfonate is the first member of a new class of tumor-specific chemotherapeutic agents for the treatment of breast cancer.