원문정보
초록
영어
It is well recognized that certain plant lectins induce apoptosis of cancer cells by interacting with cell surface glycans. Thus, it is of great importance to develop artificial glycan receptors that functionally resemble natural lectins. In this effort, apoptosis-inducing activity of two synthetic aminopyrroles that act as receptors for mannosides was evaluated. When several cancer cells were incubated with the artificial receptors, it was found that the extent of receptor-induced cell death is greater in cells expressing a high level of high-mannose oligosaccharides than in cells producing lower levels of high-mannose glycans. The ability of synthetic receptors to promote cell death was reduced in the presence of external mannosides. The results suggest that the observed cell death reflects an ability of the receptors to bind mannose expressed on the cell surface. Signaling pathway studies indicate that the synthetic receptors promote JNK activation, induce Bax translocation to the mitochondria, and cause cytochrome c release from the mitochondria into the cytosol, thus promoting caspase- dependent apoptosis. The similar phenomena were also seen in cells incubated with mannose-binding lectin ConA. Our findings serve to highlight what may be an attractive new approach to triggering apoptosis via modes of action that differ from those normally used to promote apoptosis.