Evidence from in vitro and in vivo studies suggests an association between H. pylori (HP) infection and apoptosis induction in gastric epithelial cells. Our previous study of HP-induced apoptosis showed the involvement of Bcl-2 family proteins and cytochrome c release from mitochondria. However, we did not examine the release of other factors from mitochondria, such as apoptosis inducing factor (AIF), or upstream events involving caspase-8 and Bid. Human gastric adenocarcinoma AGS cells were incubated with a cagA-pos HP strain for 0, 3, 6 and 24 h and either total protein or cytoplasmic, nuclear and mitochondrial membrane fractions were collected. Proteins were immunoblotted for AIF, Bid, PARP, caspase-8, and beta-catenin. HP activated caspase-8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time-dependent decrease in β-catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with an apparent decrease in β-actin. However, an increase in the cytoplasmic pool of AIF was seen as early as 3 h after HP exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 h, compared with the untreated controls. A band corresponding to full-length Bid was seen both in the cytoplasmic and nuclear fractions of controls, but not in cells 3, 6 or 24 h after HP exposure. These data suggest that HP might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase-8, formation of tBid, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin (Diaz et al. Cancer Res 2003, 63, 1254-61).
[Proc Amer Assoc Cancer Res, Volume 46, 2005]