Allicin induces apoptosis in EL-4 cells in vitro by activation of expression of caspase-3 and -12 and up-regulation of the ratio of Bax/Bcl-2.

Garlic (Allium sativum L.; Liliaceae) has been widely demonstrated in the role of cancer prevention, but the specific compound in garlic corresponding to this effect and its mechanisms are not clearly known. Allicin is one of the organic sulphur compounds derived from garlic. In the present study we investigated the anti-proliferative and pro-apoptotic activities of allicin in murine T-lymphocytes (EL-4) and the mechanism of inducing apoptosis in vitro. The results showed that allicin was effective in inhibiting the proliferation of EL-4 cells in vitro in a concentration-dependent manner. Further, allicin could induce the formation of apoptotic bodies, nuclear condensation, DNA spallation, and even activated the expression of caspase-3, -12 and cytochrome C (cyt C). Finally, allicin up-regulated the ratio of Bax/Bcl-2 and induced a mitochondrion membrane potential (MMP) decrease. Allicin induced apoptosis in EL-4 cells in a time- and concentration-dependent manner, in which the mitochondrial pathway might play a central role.

Calcium signals and caspase-12 participated in paraoxon-induced apoptosis in EL4 cells.

In order to investigate whether calcium signals participate in paraoxon (POX)-induced apoptosis in EL4 cells, real-time laser scanning confocal microscopy (LSCM) was used to detect Ca(2+) changes during the POX application. Apoptotic rates of EL4 cells and caspase-12 expression were also evaluated. POX (1-10nM) increased intracellular calcium concentration ([Ca(2+)]i) in EL4 cells in a dose-dependent manner at early stage (0-2h) of POX application, and apoptotic rates of EL4 cells after treatment with POX for 16h were also increased in a dose-dependent manner. Pre-treatment with EGTA, heparin or procaine attenuated POX-induced [Ca(2+)]i elevation and apoptosis. Additionally, POX up-regulated caspase-12 expression in a dose-dependent manner, and pre-treatment with EGTA, heparin or procaine significantly inhibited POX-induced increase of caspase-12 expression. Our results suggested that POX induced [Ca(2+)]i elevation in EL4 cells at the early stage of POX-induced apoptosis, which might involve Ca(2+) efflux from the endoplasmic reticulum (ER) and Ca(2+) influx from extracellular medium. Calcium signals and caspase-12 were important upstream messengers in POX-induced apoptosis in EL4 cells. The ER-associated pathway possibly operated in this apoptosis.