Dextran sulfate inhibits staurosporine-induced apoptosis in Chinese hamster ovary (CHO) cells: Involvement of the mitochondrial pathway

Abstract

Dextran sulfate has been reported to reduce cell aggregation and increase culture viability in suspension cultures of CHO cells. However, only a few of these reports have focused on the effects of dextran sulfate at the cellular level, especially with respect to cell viability. The goal of this study was to examine whether dextran sulfate inhibits CHO cell death through interference with the cellular apoptotic pathway. Apoptosis was induced using staurosporine, and the addition of dextran sulfate was shown to prevent apoptosis, as evident by a reduction in DNA laddering. Dextran sulfate also affected other events in the apoptotic pathway following the addition of staurosporine. Specifically, dextran sulfate decreased pro-caspase-9 activation, cleaved caspase-3 levels, cytochrome c release into the cytosol and mitochondrial transmembrane potential collapse. This data indicates that the mechanism by which dextran sulfate decreases staurosporine-induced apoptosis involves the mitochondrial pathway as early as cytochrome c release, but without caspase-8 activation. This study advances the understanding of the anti-apoptotic action of dextran sulfate on CHO cells and provides a rationale for the application of dextran sulfate in CHO cell culture processes.