Effect of XPO1 inhibition in cancer cells on the 3D nuclear organization of telomeres: Quantitative analysis of short-term effects.

Abstract

e22148 Background: The three-dimensional (3D) organization of the nucleus, especially the nuclear pore complex (NPC), is key to its normal function. Cancer cells have a disrupted nuclear organization that can be quantified by using 3D nuclear telomere imaging. Perturbation of NPCs can alter cell proliferation and signal transduction pathways and can lead to cancer cell death. We hypothesize that the 3D nuclear architecture of cancer cells is affected when NPCs are compromised through XPO1 inhibition by Selective Inhibitors of Nuclear Export (SINE). Methods: We used three SINE compounds; KPT-330, KPT-185, and KPT- 8602. They were individually administered at 1 μM concentration for 4 hours to proliferating cancer cell lines. The cancer cells investigated included lymphoid (Raji and Jurkat) and breast cancer cell lines (T47D and HCC1937). After four hours of incubation, the cells were 3D fixed, processed for 3D telomere hybridizations, and 3D imaged. The 3D nuclear telomere organization was measured and quan...