Diallyl trisulfide (DATS), a major garlic derivative, inhibits cell proliferation and triggers apoptosis in a variety of
cancer cell lines. However, the effects of DATS on hepatic stellate cells (HSCs) remain unknown. The aim of this study was to analyze the effects of DATS on cell proliferation and apoptosis, as well as the
protein expression profile in rat HSCs. Rat HSCs were treated with or without 12 and 24 μg/mL DATS for various time intervals. Cell proliferation and apoptosis were determined using tetrazolium
dye (MTT) colorimetric assay,
bromodeoxyuridine (
5-bromo-2'-deoxyuridine;
BrdU) assay,
Hoechst 33342 staining, electroscopy, and flow cytometry.
Protein expression patterns in HSCs were systematically studied using 2-dimensional electrophoresis and mass spectrometry. DATS inhibited cell proliferation and induced apoptosis of HSCs in a time-dependent manner. We observed clear morphological changes in apoptotic HSCs and dramatically increased
annexin V-positive -
propidium iodide negative apoptosis compared with the untreated control group. Twenty-one significant differentially expressed
proteins, including 9 downregulated
proteins and 12 upregulated
proteins, were identified after DATS administration, and most of them were involved in apoptosis. Our results suggest that DATS is an inducer of apoptosis in HSCs, and several key
proteins may be involved in the molecular mechanism of apoptosis induced by DATS.