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. 2019 Oct 7;9:14375. doi: 10.1038/s41598-019-50884-9

Figure 4.

Figure 4

Effect of TPGS and YM155 on the levels and localization of apoptotic proteins. (A) The combination of 5 μΜ TPGS and 10 nM YM155 induces Caspase 8, 9, 7 and PARP cleavage and reduces the levels of Bcl-2 and Bid following 48 hours of treatment. YM155 alone produces the appearance of the LC-II protein (the blots were cropped; full length blots are shown in Fig. S7), (B) The combination of agents increased the levels of Endo G and AIF in the cytoplasm (the blots were cropped; full length blots are shown in Fig. S8), (C) The compounds inhibit the phosphorylation of AKT. SKBR3 cells were serum starved for 24 h, followed by incubation with 5 μM TPGS and 10 nM YM155 for 3 h and treated with 1 nM insulin, 1 hour prior to protein extraction (the blots were cropped; full length blots are shown in Fig. S9). (D) Potential mechanism of action of TPGS and YM155 in breast cancer. The agents inactivate the AKT pathway leading to the downregulation of Survivin and Bcl-2 and activation of Caspase-8. MOMP is increased causing Caspase 9 and 7 cleavage and release of Endo G and AIF to the cytosol, which lead to the activation of caspase-dependent and caspase-independent PCD. The results represent the mean ± SEM of three different replicates and are representative of at least three different experiments, *P value < 0.05, **P value < 0.01, ***P value < 0.001.