Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

Abstract

Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members of the anti-apoptosis Bcl-2 family genes in several cell types has extended the knowledge of their molecular function and interaction with other proteins, and their regulation of cell death. In this review, we describe the various modes of cell death and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of anti-apoptotic engineering strategies to inhibit cell death and increase productivity in mammalian cell culture.

Beyond annexin V: fluorescence response of cellular membranes to apoptosis

“…Apoptosis is a programmed mode of cell death that is involved in a wide variety of physiological and pathological processes (Krampe and Al-Rubeai 2010;Pereira and Amarante-Mendes 2011;Ulukaya et al 2011). Detection of apoptosis is of great importance for many areas of biological research, for understanding the pathological conditions and for the development of new drugs.…”

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

“…2a). Following exposure, cells maintained their conformation, showed no signs of shrinkage, membrane damage or blebbing, key morphological signs of apoptosis, 39 indicating that exposure to polymer matrices did not result in cell damage. The effect of increasing concentrations of polymers (PVP-360, PVP-58, PVA-13-23 and PVA-9-10) on cell viability was then examined via MTS assay (Fig.…”

The Pyruvate Dehydrogenase Complex in Cancer: Implications for the Transformed State and Cancer Chemotherapy

“…There appears to be no other way to provide some of these biosynthetic resources (citrate for lipid biosynthesis, for example). Further, mitochondria are central controllers of Ca++ signaling [see 59 and references therein] and of cell death control as reviewed in [60,61]. Thus, their continued properly controlled function is likely to be essential to cancer cell homeostasis and survival.…”