Mechanism of monoclonal antibody-coupled Staphylococcus superantigen-A induced apoptosis in human bladder cancer cells.

To investigate the mechanism of apoptosis induced by BDI-1 monoclonal antibody (MAb) coupled Staphylococcal superantigen-A (SEA) in human bladder cancer cell line BIU-87. Human PBMC (effector cells) mediated cytotoxic killing of BIU-87 cells (target cells) was studied by culturing the BIU-87 cells in the presence of effector cells plus medium after their activation by treatment with SEA-targeted by MAb, SEA alone or vehicle (control). Proliferation and apoptosis of BIU-87 cells was measured after the treatments. Expression of Bax and Bcl-2 and cytokine concentration in co-culture supernatants were detected by Western blot and ELISA, respectively. Proliferation of MAb-targeted SEA BIU-87 cells decreased significantly (P < 0.05) as compared to control and SEA groups. Flow cytometry revealed apoptosis in SEA alone and more prominently in targeted-SEA treated in BIU-87 cells, which is significantly more than in controI cells (P < 0.05). In addition, Western blot analysis indicated that the ratio of Bax/Bcl-2 significantly increased by targeted SEA treatment, even at low concentration, as compared to cells treated with SEA alone or control cells (P < 0.05). However, there were no significant differences in IL-2, TNF-α and IFN-γ levels in the culture medium between SEA and targeted SEA groups, even though they are several folds higher than in control cells. SEA targeting by MAb significantly increases apoptosis in BIU-87 cells, possibly through the up-regulation of proapoptotic protein Bax and down regulation of antiapoptotic protein, Bcl-2.