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Comparative analysis of the mTOR pathway target proteins, revealed that 4EBP1 is the only protein that showed comparable levels of hyperphosphorylation at T37/46 in both the cells lines (Figure 3A).
Treatment of the spheroids with the PI3K/mTOR inhibitors alone induced significant cell growth inhibition and ATP drop in both the cells lines.
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Despite 51 STSs encompassing AZFa, AZFb and AZFc screened in this study, no microdeletions were detected suggesting that MSY remained intact in both the cell lines.
As shown in Fig. 2b, a statistically significant increase in cleaved PARP was seen in both the cell lines (p < 0.01).
As in the previous work, both the cell lines showed synergistic responses to dual inhibition.
MitoT also significantly attenuated EO-induced injury to both the cell line and the primary AM including diminishing mROS and improving Δ ψm.
In initial screening, analogs 5, 14 and 15 were found to be much more effective than the standards against both the cell lines.
These results were further substantiated by the dose-dependent down-regulation of the EMT-associated transcription regulators, Snail and Zeb-1, upon Irigenin treatment in both the cell lines (Fig. 3).
Metabolite 2 was found to be moderately active against both the cell lines.
Both the cell lines displayed consistent biochemical characteristics across in vitro, in vivo, and ex vivo analyses.
a, b Indeed treatment of H295R (a) and SW-13 (b) cells with nutlin-3 and BI-2536 sensitized both the cell lines to nutlin-3.
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