| Popis: |
The antineoplastic drug rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) has been hypothesized to interfere with tumor cell proliferation by affecting energy metabolism and mitochondrial function. In this study, the intracellular targets of rhein were investigated in the A431 epithelial cell line by means of biophysical and structural techniques. After treatment with 50 microM rhein at different times (8 and 24 hours), a series of remarkable morphological modifications ultimately leading to irreversible cell injury was observed. In particular, scanning and transmission electron microscopic observations point to the cell surface and mitochondria as probable targets of this drug. In addition, biophysical analyses conducted by electron paramagnetic resonance (EPR) spectroscopy seem also to indicate that cellular membranes are a direct target in rhein-induced damage. Concomitantly the cytoskeletal network underlying the inner leaflet of the plasma membrane (the microfilament system) also underwent a rearrangement. Taken together, the effects induced by rhein presented here seem to indicate that this drug, as well as other anthraquinones or other compounds that selectively impair energy metabolism, can act on neoplastic cells by probably altering cell membrane function and membrane-associated cytoskeleton. |
