Protein A-induced apoptosis of cancer cells is effected by soluble immune mediators

Since Protein A (PA) of Staphylococcus aureus has been documented to have both antitumor and immunostimulatory properties, we attempted to determine whether PA-induced tumor cell death was effected through the immune system of the host, and analyze the mechanisms of such anti-tumor activity. For in vivo studies, Ehrlich's ascites carcinoma (EAC) cells were inoculated into the peritoneal cavity of Swiss albino mice. PA (1 micro g/20 g body weight) was injected biweekly for 2 weeks. To determine the role of immunomodulators in PA-induced tumor cell death, EAC were co-cultured with PA-primed splenic cells or with the spent medium of the same. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells, by PA, i.e. (1) activation of the immune system of the host to release different apoptogenic factors like tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO); and (2) induction of EAC apoptosis by these soluble immune mediators through the up-regulation of pro-apoptotic factors (p53 and Bax) and down-regulation of anti-apoptotic factor (Bcl-2), resulting in the activation of caspase-3. The present observations provide additional findings on an approach to cancer immunotherapy that causes apoptogenic insult to cancer cells.