Ment inhibited prenylation of all isoforms of Ras and Ras to ERK, w While BMS was ineffective against 214 662 Ras and ERK K PP. These observations are consistent with the specificity of t L dual enzyme RAAS System reported 778 123. Although the combination of L IPR has entered 778 123 with idarubicin Born a synergistic inhibition of proliferation in K562 analyzed KG1a and THP 1 cells gr Th part of the area was thecombination FTI BMS 214662 with idarubicin only partially synergistic in the range of h Higher doses. Interestingly, Karp et al. reported that the partial synergy of FTI R115777 and Top2 inhibitor etoposide in HL-60 cells at concentrations that the IC50 and the combination of an antagonist effect exceeded below the IC50. Has entered the pre-treatment and the simultaneous L 778123 and idarubicin Withidarubicin born in less apoptosis in cells treated alone, had w While BMS 214 662 no effect on idarubicin-induced apoptosis. This is likely The DPI 778 123 induced reduction Top2mRNA and protein expression. Another reason for this observation k Be nnte that the Department of L caused a G1 arrest 778 123 and is cytotoxic in these cells, w While the FTI BMS 214 662 induces apoptosis. Our results in HL-60 cells for a r For the Ras signaling pathway in the cytotoxicity t of idarubicin and recall that previous studies have shown that lovastatin to protect the cells from two other Top2 inhibitors, doxorubicin and etoposide. Lovastatin is an HMG-CoA reductase, the cellular geranylgeranylpyrophosphate Ren storing farnesyl pyrophosphate and thus prevents both FTase consumed and mammalian cells GGTases I and II resistance to drugs targeting Top2 in S Is h Frequently with reduced Top2 / expression associated what suggesting that the resistance due to the reduced enzyme DNA-Sch ending mediation. Therefore, treatment resulted in 778 123 L decreased significantly and Top2 Top2 Top2 mRNA and protein levels in HL-60 cells, thus reducing the effect of idarubicin in combination therapy.
Others have reported that Top2 and Top2 decreased protein expression in K562 idarubicin and mitoxantrone-resistant cells. Reduction Top 2 mRNA and protein have been induced by L 778 123 k nnte Due to the drug’s reduced G1 cell cycle arrest effects of Ras and ERK. These differences, as is not the exact mechanisms of action of these drugs is known, led us to hypothesize that the combination of both prenyltransferase inhibitors k Can rdern f cell death. Our results show that the combination of these two chemically different prenyltransferase inhibitors have led to an almost completely Requests reference requests getting blockade of protein Pazopanib prenylation and the synergistic inhibition of cell proliferation of Leuk Chemistry. Zus Tzlich showed cells with FTI / dpi combination treatment significantly increased Ht caspase activation, PARP cleavage and DNA fragmentation. We analyzed the treated cells with modulation of prenylation in the prenyltransferase inhibitors alone or in combination and found that the FTI BMS 214 662 not only inhibit the prenylation of some proteins with low molecular weight such as Ras and K Cdc42. It was not unexpected that these proteins Are known to undergo alternative geranylgeranylation order. The CIO almost 778 123 YOUR BIDDING inhibited prenylation of Ras N and K, but not RhoB or RhoC block prenylation, either alone or in combination with BMS-214662nd He.