FIG. 6.

Cytotoxic effects of Simvastatin on NPC cells. (a) C15 and C17 cells derived from xenografted tumors were short-term cultured for 5 days on a polyHEMA matrix in culture medium supplemented with vehicle (DMSO) only or various concentrations of Simvastatin. Cell viability was measured at days 1, 3, and 5 using a soluble form of MTT (see Materials and Methods). (b) Low-magnification electron micrographs showing one example of a C15 cell treated for 5 days with 5 μM Simvastatin and several control cells incubated with the vehicle (DMSO) by itself. Among the morphological changes induced by Simvastatin, note the loss of cellular connections, the transition to round-shaped cells and nuclei, the intense vacuolization, and the partial chromatin condensation at the periphery of the nucleus. (c) Assessment of PARP cleavage in C15 cells treated by Simvastatin (Sim) or the vehicle (DMSO) by itself. Thirty micrograms of protein derived from whole-cell extracts was loaded per lane. A positive control was provided by C15 cells treated with a Fas agonist for 12 h (7C11; 250 ng/ml); this sample contains the cleaved (89 kDa) in addition to the uncleaved (115 kDa) form of PARP.