Induction of caspase-dependent chromatin disassembly in DFF40/CAD-deficient glioblastoma-derived cells

Apoptosis, a tightly regulated cell death program, involves a caspase-triggered cascade of biochemical and morphological events. The activation of Caspase-Activated DNase (CAD), or DFF40, is considered to be the key event allowing dying cells to show classical apoptotic nuclear changes. Apoptotic nuclear morphology is characterized by chromatin condensation into highly packaged round masses and fragmentation of the nucleus. We have previously reported that human glioblastoma (GBM)-derived cells, an extremely aggressive solid brain tumor, holds an intrinsic defect in DFF40/CAD expression1. Thus, the natural behavior of GBM cells when challenged with different cytotoxic compounds is to show a unique mass of compacted chromatin in the absence of nuclear fragmentation2. However, H&E-stained histological sections from GBM-affected patients revealed several malignant cells showing spontaneous condensation and fragmentation of the nucleus. In this sense, GBM-cultured cells switched its predominant nuclear aspect to a DFF40/CAD-dependent apoptotic nuclear morphology upon an adequate activation of caspases. Therefore, besides GBM cells are deficient in DFF40/CAD expression, the endonuclease can be efficiently activated.