Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wnt/β-Catenin Pathways

Figure 2

3-Cl-AHPC-mediated inhibition and degradation of pancreatic cancer stem cells spheres of CD133⁺, CD44⁺/CD24⁺/EpCAM⁺, and stem-like spheres of CD44⁺/CD24⁺ PANC-1 cells. ((a), (b) and (c), (d)) 3-Cl-AHPC and AHP3 exposure resulted in inhibition of CD44⁺/CD24⁺/EpCAM⁺ and CD133⁺ cells growth and sphere formation and degradation of the derived spheres. ((e), (f)) AHP3 and 3-Cl-AHPC inhibited sphere formation and inhibition of growth and degradation of the CD44⁺/CD24⁺-derived spheres. For sphere formation, the CD44⁺/CD24⁺/EpCAM⁺, CD133⁺, and CD44⁺/CD24⁺ cells were sorted by flow cytometry and approximately 200–300 cells were seeded with B27 containing DMEM/F12 medium in 96-well low attachment plates and 1 μM 3-Cl-AHPC or AHP3 added either the day after seeding or 7 days following sphere formation. The sizes of spheres were photographed and measured on a 100 μm scale and magnification 400X using Olympus fluorescence microscope digital camera software and DP2-BSW software. The error bars represent the mean of 15 sphere determinations ± the standard deviation. ** was significantly different in comparison to control spheres. Data were analyzed by ANOVA, Tukey HSD test for multiple comparisons. **𝑃<0.01 versus control.

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