G pathways as previously described in DAVID database. EASE value of 0.1 was set to determine the significance of geneterm enrichment in DAVID annotation system. A gene list of 14065 and 11342 differentially (-)-Blebbistatin chemical information expressed genes from both cell lines were selected for further evaluation. Similar Drug Response to Cancer Cell Lines between Gossypol and AT101 Three gastric cancer cell lines were treated with gossypol and AT101 to determine their IC50, respectively. As expected, -gossypol was more potent than racemic gossypol but there were generally less than 10fold differences in IC50 between both drugs in gastric cell lines. All subsequent in vitro studies were carried out using the racemic gossypol as there was little difference in cellular cytotoxicity using either drug. Gossypol was found to have moderate activity in all the ten cell lines. Unlike gemcitabine, there was no clear association between the level of Bcl-2 expression in the cell lines to the IC50 of the drug. Synergistic Drug Interaction between Gossypol and Gemcitabine in Gemcitabine-resistance Cell Line with High Bcl-2 Expression To determine the possible synergism interaction between gossypol and gemcitabine, combination drug treatment were carried out in all 10 cancer cell lines. With the exception of SNU1, synergism was observed in the cell lines that had high Bcl-2 expression, but not in cell lines that expressed low Bcl-2 IC50 of gemcitabine to breast cancer cell lines. Mean IC506Standard Error of at least two independent experiments were performed in triplicates. Cells were treated with gemcitabine for 72 hr and cell proliferation was assessed using the MTS assay. Immunoblot of Bcl-2 baseline expression in breast cancer cell lines. doi:10.1371/journal.pone.0050786.g002 drug treatment. Collectively, these observations suggested that gossypol reversal of gemcitabine resistance involves the downregulation of anti-apoptotic proteins and upregulation of pro-apoptotic proteins. Reversal of Gemcitabine Resistance by Gossypol was Associated with Up-regulation of Noxa and Downregulation of Bcl-2 and Bcl-xl To investigate the underlying molecular mechanisms of synergistic interaction between gossypol and gemcitabine, we examined the changes of pro-apoptotic and anti-apoptotic proteins in high Bcl-2 expression GEM-R cell lines. As shown in Significant Changes in Apoptotic Pathway Contributed to Differential Response to Gemcitabine and Gossypol Whole genome expression profiling was carried out in SNU1 and CNE2 to evaluate alternative mechanisms for their differences in drug response to gemcitabine alone and gemcitabine/gossypol combination. A total of 2702 genes were differentially expressed in pre- and post-treatment samples and was mapped to 61 enriched biological processes using KEGG pathway analysis. The most significant biological processes regulated by these genes include spliceosome, cell cycle, pyrimidine metabolism, p53 signalling and apoptotic pathways has been widely studied with respect to plant food allergenic reactions and their role in food and/or pollen cross-reactivities. Allergens from this family have been found in most vegetable sources. Pru p 3, the peach LTP, is the model member of this family. It is recognized by 75% of patients who suffer from peach allergy, the most frequent plant food allergy in Spain. Pru p 3 has been implicated in food cross-reactivities, especially those involving fruits and nuts, and pollens such as those of mugwort and plane. The princip
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