Differential Effects of Pravastatin and Simvastatin on the Growth of Tumor Cells from Different Organ Sites
Figure 5
Incorporation and growth response of normal hepatocytes or tumor cells to hydrophilic-pravastatin or hydrophobic-simvastatin.
A & B) Total ion chromatography methods were developed to attain critical separation profiles showing pravastatin and simvastatin. C) Mass spectroscopy was performed by using deuterated standards as internal controls for separation to distinguish between statins. Statins were detected by using electrospray-negative ionization and monitoring by magnetic resonance microscopy. Fragmentation of the statins were performed using argon as the collision gas at a collision cell pressure of 2.1×10−3 torr. D) LS/MS/MS determination of statins. Monolayers of normal hepatocytes or prostate cancer cells (PC-3) were placed in fresh serum-free medium before the addition of 10 µM pravastatin or simvastatin. Cell culture medium and cells were collected 6 h after treatment. The statins were subjected to solid-phase extraction and analyzed for the presence of pravastatin or simvastatin by LC/MS/MS analysis. Data represent two determinations run in duplicate. E) Effects of pravastain and simvastatin on OATP expressing human hepatocytes were determined by MTT assay and are represented as a percent of the control absorbance at a wavelength of 540 nm. Data shown are from representative experiments (n = 8). These data illustrate that both pravastatin and simvastatin suppressed the growth of hepatocytes to nearly the same extent. Values are expressed as mean+SD. * p<0.05, significant difference between control and simvastatin or pravastatin groups. ¶ p<0.05, significant difference between simvastatin and pravastatin groups.