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. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Cancer Res. 2015 Feb 20;75(7):1423–1432. doi: 10.1158/0008-5472.CAN-13-3451

Figure 5. ONC201/TIC10-mediated induction of surface TRAIL in CSCs involves inhibition of Akt and ERK followed by Foxo3a activation.

Figure 5

(A) ONC201/TIC10 inhibits Akt, ERK and activates Foxo3a in CSCs. Sorted DLD1 Aldefluor(+) cells were subcutaneously injected into the right and left flank of athymic nude mice. Upon tumor formation, mice were administered either vehicle or ONC201/TIC10 50 mg/kg (i.p.). Tumors were harvested after 72 h of treatment and western blot analysis was performed (B) Western blot analysis of sorted Aldefluor(+) (CSC) and unsorted (non CSC) SW480 cells treated with DMSO or 5 μM ONC201/TIC10 for 72 h (C) Parental (WT) or myristoylated- (myr-) Akt overexpressing HCT116 cells were treated with DMSO or 5 μM ONC201/TIC10 for 72 h. CD44 staining was detected by flow cytometry. Fold depletion is the ratio of % CD44(+) cells in DMSO and ONC201/TIC10 treatment groups. * indicates p < 0.02. (D) WT or myr-Akt overexpressing HCT116 cells were treated with DMSO or 5 μM ONC201/TIC10 for 60 h. Aldefluor(+) cells were detected by flow cytometry. Fold depletion is the ratio of % Aldefluor(+) cells in DMSO and ONC201/TIC10 treatment groups. * indicates p < 0.0005. (E) WT or myr-Akt overexpressing HCT116 cells were treated with DMSO or 5 μM ONC201/TIC10 for 72 h. CD44 and TRAIL staining was detected by flow cytometry. Fold induction is the ratio of % CD44(+)TRAIL(+) cells in ONC201/TIC10 and DMSO treatment groups. * indicates p < 0.05.