Induction of apoptosis with diallyl disulfide in AGS gastric cancer cell line

Abstract

PurposeDiallyl disulfide (DADS) is a major organosulfur compound derived from garlic. It has been reported that DADS is able to inhibit the proliferation of several tumor cells. In this study, the effect of DADS was investigated in terms of the proliferation of AGS, gastric adenocarcinoma cell line at various concentrations.MethodsThe viability of cultured cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To detect the induction of apoptosis, Annexin V-FITC/propodium iodide (PI) staining assay was performed. Analysis of reactive oxygen species (ROS) and the distribution of cells in the cell cycle were measured by a flow cytometer. And using the Western blot analysis, the change of Fas, caspase-3, Bax, Bcl-2 activity was measured.ResultsThe percentage of live AGS cells was decreased to 23% of that in the control group after 400 µM DADS treatment for 48 hours. The Annexin V positive/PI negative (apoptosis portion) area increased from low concentration of DADS to high concentration. When comparing among the DADS treatment groups, the amount of ROS production increased in a dose dependent manner. The percentage of sub-diploid DNA content increased from 8.71% at 50 µM to 25.74% at 400 µM DADS treatment group. The expressions of Fas, caspase-3, Bax were increased and that of Bcl-2 was decreased in a dose dependent manner.ConclusionDADS decreases the viability of AGS cell lines and induces apoptosis in a dose-dependent manner. But the relationship of the anti-proliferative effect of DADS and related molecular changes were not clearly proportional to the concentration of DADS.

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“…Therefore, Annexin V was used for detecting apoptosis. 22) The results in Fig. 6 by FACS analysis showed % apoptosis of ARPE-19 with normal glucose, high glucose and high glucose plus the polysaccharide in 2.14%, 27.95%, 7.88% respectively indicating that the polysaccharide compound prevented ARPE-19 cells from apoptosis caused by high glucose.…”

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“…Potential of DADS as a powerful antioxidant (Na et al 2012, Wu et al 2005) and anticancer agent (Lee et al 2011, Liao et al 2009, Yang et al 2006) is very well-documented. Significant efficacy gets hindered by some limitations like low oral bioavailability (Germain et al 2002).…”

“…The Bcl-2 family of proteins includes antiapoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), as well as a number of pro-apoptotic molecules (Bax, Bad and Bim), whereas overexpression of the antiapoptotic protein Bcl-2, blocks mitochondrial outer membrane permeabilization, and inhibits apoptosis (Elumalai et al 2012, Gillings et al 2009, Tait and Green 2010. DADS has been well-documented in inducing the intrinsic apoptosis pathway (Lee et al 2011, Lei et al 2008. The molecular mechanisms of apoptosis by the DADS and DADS-SLN were explored in the MCF-7 cells by Western blot.…”

“…Allium species include garlic, onion, leeks, chives, and scallions which have great potential in treatment/prevention of cancers and cardiovascular diseases. Among them garlic has demonstrated antitumor, antihypertensive, and antihypercholemic actions (Lee et al 2011). Epidemiological studies reported that dietary intake of allium products is inverse to the risk of many cancers.…”

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