Apoptosis of rat hepatic stellate cells induced by diallyl trisulfide and proteomics profiling in vitro.
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.
a Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Yajie
Y
Zhang
a Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Xiaoming
X
Zhou
b Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University College of Pharmacy, Guangzhou, Guangdong Province, China.
Lipeng
L
Xu
c Center of Community Health Services, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China.
Lulu
L
Wang
d Department of Digestive System Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China.
Jinling
J
Liu
d Department of Digestive System Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China.
Jing
J
Ye
e Department of Pharmacology, Zhong-Shan Medical College, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Pengxin
P
Qiu
f Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China.
Qinghua
Q
Liu
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005737:Garlic / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D013440:Sulfides; C042577:diallyl trisulfide
apoptose; apoptosis; cellules de Kupffer; diallyl trisulfide; differentially expressed proteins; hepatic stellate cells; protéines exprimées de façon différentielle; trisulfure de diallyle