Journal
ANTI-CANCER DRUGS
Volume 20, Issue 8, Pages 702-712Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e32832e89c7
Keywords
apoptosis; diallyl trisulfide; osteosarcoma; proteome
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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 mu mol/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 mu mol/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 G(0)/G(1) 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. Anti-Cancer Drugs 20:702-712 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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