Pro-apoptotic and immunomodulatory activity of a mycobacterial cell wall-DNA complex towards LNCaP prostate cancer cells

BACKGROUND. We have isolated a mycobacterial cell wall-DNA complex (MCC) po ssessing anti-cancer activity against bladder cancer cells. The anti-cancer activity of MCC appears to be due to two effects: a direct interaction wit h bladder cancer cells resulting in the induction of apoptosis and an indir ect effect via the stimulation of monocytes and macrophages cytokine synthe sis. In this study, the direct effect of MCC towards LNCaP cancer cells was evaluated. METHODS. Inhibition of proliferation, cell cycle arrest and induction of ap optosis were evaluated in vitro using LNCaP cells treated with MCC. The syn thesis of IL-12, GM-CSF, and TNF-alpha by LNCaP cells in response to MCC wa s also determined. Experiments were performed to gain insight into the mech anism of action of MCC towards LNCaP cells. RESULTS. MCC caused a dose-dependent inhibition of the proliferation of LNC aP cells that was associated with cell cycle arrest at the G0/G1 phase. MCC -induced apoptosis of LNCaP cells was consistent with a mitochondrial pathw ay involving mitochondrial disruption, release of cytochrome c, and an incr ease in Bax protein levels leading to caspase-3 and -7 activation and cleav age of poly (ADP-ribose) polymerase and nuclear mitotic apparatus protein. Surprisingly, MCC also directly induced the synthesis of IL-12 and GM-CSF, but not TNF-alpha, by LNCaP cells. CONCLUSIONS. MCC possesses the ability to directly induce apoptosis of LNCa P cells and to trigger the synthesis of IL-12 and GM-CSF by these cells, su ggesting a potential role of MCC for the treatment of prostate cancer. (C) 2001 Wiley-Liss, Inc.