Lysosome: as a proposed target for rose bengal in inducing cell death in melanoma cells
We have previously shown that rose bengal (RB) itself and not as a photosensitiser could induces dual modes of cell death in melanoma cells and has clinical activity against melanoma. But the mechanisms of RB-induced cell death are unclear. Recently lysosome was reported to initiate different kinds of cell death including necrosis, caspase-dependent and -independent apoptosis. The hypothesis of this study is to investigate the role of lysosome in mediating RB-induced cell death in melanoma cells focusing on lysosomal protease cathepsin B (CB). We present two lines of evidence indicating a central role for the CB in mediating cell death. First, inhibition of CB would result in a strong protection against drug-induced cell death and apoptosis in melanoma cells. Simultaneous inhibition of caspases would determine that CB acts upstream or downstream the caspase cascade. Second, we show RB triggers disruption of lysosomes leading to release and activation of CB using an engineered yellow fluorescent protein-tagged CB. It is hypothesized that RB-induced cell death in melanoma cells is mediated through lysosomal CB in this novel cell death pathway. This idea points to a new tumor-suppressive role for lysosomes which may be less affected by chemotherapy-induced resistance mechanisms.
Journal of Medical Hypotheses and Ideas, Volume:2 Issue:2, 2008
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