MEMBRANE AND CYTOSKELETON ARE INTRACELLULAR TARGETS OF RHEIN IN A431 CELLS

The antineoplastic drug rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) has been hypothesized to interfere with tumor cell proliferatio n by affecting energy metabolism and mitochondrial function. In this s tudy, the intracellular targets of rhein were investigated in the A431 epithelial cell line by means of biophysical and structural technique s. After treatment with 50muM rhein at different times (8 and 24 hours ), a series of remarkable morphological modifications ultimately leadi ng to irreversible cell injury was observed. In particular, scanning a nd transmission electron microscopic observations point to the cell su rface 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 dir ect target in rhein-induced damage. Concomitantly the cytoskeletal net work underlying the inner leaflet of the plasma membrane (the microfil ament system) also underwent a rearrangement. Taken together, the effe cts induced by rhein presented here seem to indicate that this drug, a s well as other anthraquinones or other compounds that selectively imp air energy metabolism, can act on neoplastic cells by probably alterin g cell membrane function and membrane-associated cytoskeleton.