Caspase-independent cell death by allicin in human epithelial carcinoma cells: involvement of PKA

Allicin, the major component of Garlic (Allium sativum) was examined for the ability to induce apoptosis and the mechanism of the induction of apoptosis in human epithelial carcinoma cells. Allicin inhibited cell growth and induced apoptosis in gastric epithelial cells. Treatment with allicin resulted in morphological changes, DNA fragmentation, hypodiploid DNA contents and the translocation of Bax to mitochondria. The release of cytochrome c from mitochondria into the cytosol, which is an initiator of the activation of caspase cascades, was observed in allicin-treated cells. However, pretreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), a broad spectrum of caspase inhibitor, could not rescue apoptotic cells from allicin toxicity. Coincidently, caspase-3 activation and cleavage of PARP were not detected. In addition, caspase independent apoptosis-inducing factor (AIF) was released from mitochondria after treatment with allicin. After pre-incubation of cells with the protein kinase A (PKA) inhibitor H-89, allicin was not capable of inducing an increase of the rate of apoptosis with affecting the expression levels of Bax and AIF. These data demonstrate that allicin induces a caspase-independent apoptotic pathway mediated by mitochondrial release of AIF and PKA appears to be involved in allicin-induced apoptosis in gastric epithelial cells.