Diallyl Trisulfide Inhibits Leptin-induced OncogenicSignaling in Human Breast Cancer Cells but Fails toPrevent Chemically-induced Luminal-type Cancer in Rats

ABSTRACT

Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide (DATS) on growth of breast cancer cellsin vitro and in vivo. This study investigated the effect of DATS on oncogenic signaling regulated by leptin, which plays an importantrole in breast carcinogenesis. Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in thepresence of DATS in MCF-7 (a luminal-type human breast cancer cell line) and MDA-MB-231 (a basal-like human breast cancer cellline). Leptin-stimulated cell proliferation, clonogenic cell survival, and migration and/or invasion ability in MCF-7 and/or MDA-MB-231cells were also suppressed by DATS treatment. DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2, Bcl-xL, Cyclin D1, vascular endothelial growth factor, and matrix metalloproteinase-2. Western blotting revealeda decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when comparedto controls in vivo. However, the incidence of N-methyl-N-nitrosourea-induced luminal-type breast cancer development in rats wasnot affected by oral administration of 5 mg/kg or 25 mg/kg DATS. The present study reveals that oncogenic signaling induced byleptin is inhibited in the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity.