Mechanisms of Action of Diallyl Trisulfide in Breast Ductal Carcinoma In Situ Cells

Objectives Breast ductal carcinoma in situ (DCIS) is an early stage, localized form of breast cancer that can progress to an invasive breast cancer phenotype. Diallyl trisulfide is a bioactive organosulfur compound derived from Allium vegetables that has been shown to have anticancer effects in various cancer models. We have previously shown that diallyl trisulfide inhibits alpha secretases and Notch signaling pathway components in breast cancer cells. The objective of this study was to investigate the mechanisms of action of diallyl trisulfide in breast DCIS cells, with a primary focus on characterizing the induction of apoptosis in breast DCIS cells. Methods Breast DCIS cells SUM102PT [ER(−) and PR(+)] and SUM225CWN [ER(−) and PR(−)] were used in this study. Clonogenic assay was used to determine the colony formation ability of DCIS cells exposed to diallyl trisulfide. Apoptosis was quantified using a cell death detection ELISAPLUS kit from Roche according to the manufacturer's instructions. Western immunoblotting was used to determine the effect of diallyl trisulfide on apoptosis molecular markers. Results Diallyl trisulfide, a bioactive compound derived from Allium vegetables, induced a dose-dependent reduction in colony formation ability of breast DCIS cells. Diallyl trisulfide inhibited DCIS cell growth by inducing apoptosis as shown by a dose-dependent increase in DNA fragmentation as determined by ELISA assay. Induction of apoptosis was more pronounced in SUM102PT cells than in SUM225CWN cells at similar concentrations of diallyl trisulfide. Induction of apoptosis was characterized by a dose-dependent increase in cleaved PARP, cleaved caspase 3, and cleaved caspase 7. Expression levels of anti-apoptotic proteins Bcl2 and p-Bcl2 were decreased in DCIS cells exposed to diallyl trisulfide in a dose-dependent manner. Conclusions Diallyl trisulfide inhibits growth and induces apoptosis in breast DCIS cells. This study supports further investigation of diallyl trisulfide as a potential chemopreventive agent for breast DCIS. Funding Sources This work was supported by the USDA National Institute of Food and Agriculture, Hatch project NEV00765. Core facility used for research was supported by NIH grant P20 GM103650.