All subsequent experiments were carried out using 8 ug mL lovastatin in its lactone or acid form. In rescue experiments, when cells were co incubated with lovastatin and GGPP, FPP or mevalonate, only mevalonate http://www.selleckchem.com/products/ganetespib-sta-9090.html and GGPP were able to fully rescue cells from the anti proliferative effect of lovastatin, whereas FPP could only achieve a partial rescue. Upon GGPP and mevalonate co exposure with 8 ug mL lovastatin, cells regained 92 to 98% of the prolif eration rate of control cells, Inhibitors,Modulators,Libraries whereas only 67% was regained with the co administration of lovastatin and FPP. Two dimensional gel electrophoresis and MS analysis of lovastatin induced changes in the protein expression of breast cancer cells In order to obtain a comprehensive view of changes in the protein synthesis in response to lovastatin treatment, proteome analyses using two dimensional gel electro phoresis were performed on MDAMB468 and MDAMB231 breast cancer cell lines.
Both forms of lovastatin were used for cell treatment. Functional classification of identified proteins Each identified protein was assigned a functional classifi cation based on the gene ontology annotation in the Database for Annotation, Visualization, and Integrated Discovery. The DAVID annotation tool was Inhibitors,Modulators,Libraries used for functional clustering and pathway mapping of identified protein hits. A comparison between the expressional changes of spots in the lactone or hydroxy acid group revealed that both chemical forms of lovasta tin followed the same directional change through an increase or decrease in Inhibitors,Modulators,Libraries the relative protein abundance.
For this reason, we combined the treatment groups Inhibitors,Modulators,Libraries and these combined protein hits were then subjected to DAVID annotation tool analysis. Seventy four proteins were identified as significantly changed upon treatment with 8 ug mL lovastatin in MDAMB231 cells, and 42 such proteins were identified in MDAM468 cells. Despite the stronger response of MDAMB231 cells, impact by lovastatin on the biological processes was Inhibitors,Modulators,Libraries similar in both cell lines. For example, the addition of lovastatin not only influenced the major metabolic cellu lar pathways, such as glycolysis or pentose phosphate shunt, it also changed expression of proteins involved in the regulation of apoptosis, stress response, cell differen tiation and actin filament morphogenesis. Furthermore, lovastatin lactone and http://www.selleckchem.com/products/arq-197.html acid exposure induced changes in cell cycle regulatory proteins and small GTPases mediated signal transduction members. Small GTPases mediated signal transduction Small GTPase family members, some of which are known to modulate Ras protein signal transduction, have been described in the literature as major targets of statins other than HMG CoA reductase. Our proteomics data revealed a decrease in total expression of RhoA.