Cell Apoptosis Assays for Drug Discovery

Apoptosis, or programmed cell death, is a highly regulated way for an organism to selectively eliminate cells. This process plays an important role in embryogenesis, maintaining an organism’s size, and eliminating damaged or aberrant cells. The importance of apoptosis in human health is underscored by the many diseases resulting from aberrant apoptosis. Dysregulation of apoptosis has been linked to various cancers, neurological and cardiovascular disorders, and autoimmune diseases.

Cell death is required for many normal physiological functions for both development and homeostasis. The ability of tumor cells to elude programmed cell death, also known as apoptosis, is a hallmark of most types of cancer. A wide variety of cellular proteins, including cell surface receptors, adaptors, proteases and mitochondrial components, regulate a fine balance between cell survival and death by apoptosis. Mutations of these sensor and/or effector proteins may tip the balance, resulting in the uncontrolled survival and proliferation of cancer cells. Uncovering apoptosis mechanisms will result in new strategies to exploit apoptosis for therapeutic benefit.

Some of Apoptosis Assay Platforms:

– Annexin V Binding Assays
– Caspase Activity Assays
– Mitochondrial Membrane Potential Assays
– DNA Fragmentation and Morphology

Why use apoptosis assays in drug development?

– Standard end point proliferation assays do not allow for accurate analyses of the cell killing capacity of compounds, i.e. they do not clearly differentiate between cytostatic and cytotoxic compounds;
– Apoptosis is a highly dynamic process that can be missed if the wrong time-point is selected in a single readout assay;
– Monitoring apoptosis induction over time provides useful data that can be applied to follow-up assays to study apoptotic cascade.

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