A proteomic study on a human osteosarcoma cell line Saos-2 treated with diallyl trisulfide

Abstract

Garlic is generally used as a therapeutic reagent against various diseases, and numerous studies have indicated that garlic and its derivatives can reduce the risk of various types of human cancer. Diallyl trisulfide (DATS), a major member of garlic derivatives, could inhibit the cell proliferation by triggering either cell cycle arrest or apoptosis in a variety of cancer cell lines as shown in many studies. However, whether DATS has the same effect on human osteosarcoma cells remains unknown. In this study, we have attempted to analyze the effects of DATS on cell proliferation, cell cycle, induction of apoptosis, global protein expression pattern in a human osteosarcoma cell line Saos-2 cells, and the potential molecular mechanisms of the action of DATS. Saos-2 cells, a human osteosarcoma cell line, were treated with or without 25, 50, and 100 micromol/l DATS for various time intervals. The cell proliferation, cell cycle progression, and apoptosis were examined in this study. Then, after treatment with or without 50 micromol/l DATS for 48 h, protein add pattern in Saos-2 cells were systematically studied using two-dimensional electrophoresis and mass spectrometry. DATS could inhibit the proliferation of Saos-2 cells in a dose-dependent and time-dependent manner. Moreover, the percentage of apoptotic cell and cell arrest in G0/G1 phase was also dose-dependent and time-dependent upon DATS treatment. A total of 27 unique proteins in Saos-2 cells, including 18 downregulated proteins and nine upregulated proteins, were detected with significant changes in their expression levels corresponding to DATS administration. Interestingly, almost half of these proteins (13 of 27) are related to either the cell cycle or apoptosis. DATS has the ability to suppress cell proliferation of Saos-2 cells by blocking cell cycle progression and inducing apoptosis in a dose and time-dependent manner. The proteomic results presented, therefore, provide additional support to the hypothesis that DATS is a strong inducer of apoptosis in tumor cells. However, the exact molecular mechanisms, how these proteins significantly changed in the Saos-2 cell line upon DATS treatment, should be further studied.

Anticancer Mechanism of Sulfur-Containing Compounds

“…Two proteomic investigations provide additional support to this evidence by showing that organosulfide-sensitive proteins are tightly associated with apoptotic pathways [32,33]. The available data demonstrate how modulation of Bcl-2 family, activation of stress signaling cascades, activation of p53, generation of reactive oxygen species (ROS), changes in calcium homeostasis, and microtubule depolymerization are all implicated in the apoptotic response of cancer cells to Allium sulfur compounds (Fig.…”

Surface proteomic analysis of osteosarcoma identifies EPHA2 as receptor for targeted drug delivery

“…Previous research includes efforts to unravel OS development, to study mechanisms of drug response, to identify new biomarkers for prognosis and therapy response, and, to identify putative therapeutic candidates for OS by studying differences within the entire proteome of OS cells or cell lines compared with human osteoblasts (Guo et al , 2007a; Folio et al , 2009; Liu et al , 2009; Zhang et al , 2009). …”

“…Cell surface molecules are known to be involved in important biological processes, including proliferation, differentiation, migration and survival (Stevens and Arkin, 2000; Wu and Yates, III, 2003; Scheurer et al , 2005; Lund et al , 2009; Zhang et al , 2009). Also, surface molecules such as growth factor receptors, cytokines, metalloproteases and integrins are implicated in the development and progression of malignancies, including OS (Khanna et al , 2004; Krishnan et al , 2005; Kansara and Thomas, 2007; Guo et al , 2008; Kim et al , 2008; Wan et al , 2009; Rubin et al , 2010).…”

In Vitro Efficacy of Diallyl Sulfides against the Periodontopathogen Aggregatibacter actinomycetemcomitans

“…Garlic oils contain major organosulfur compounds, including diallyl sulfide (DAS; 112 g/g), diallyl disulfide (DADS; 1,183 g/g), and diallyl trisulfide (DATS; 751 g/g), and minor amounts of many other volatile compounds (49). These compounds possess potent anticancer, antioxidant, and anti-inflammatory immune modulation activities and antimicrobial properties (2,30,71,72,79,83). The inhibitory effect of DASs against Bacillus cereus, Salmonella sp., and Vibrio cholerae (7,62,63), Staphylococcus aureus and Candida albicans (42,51), Helicobacter pylori (52,58), and Klebsiella pneu-moniae and Pseudomonas aeruginosa (17,37,53,73) were studied, and a recent report has shown that DASs were synergistically effective when combined with antibiotics against antibiotic-resistant strains of Escherichia coli, Enterobacter cloacae, E. faecalis, and Citrobacter freundii (80).…”