Resisting Apoptosis NZ
In their seminal paper ‘The Hallmarks of Cancer’, Weinberg and Hanahan (2000, 2011) organized the complexities of cancer into key underlying principles and suggested that exploring these hallmarks will support the development of new and improved cancer therapies. ‘Resisting Apoptosis’, is an original hallmark that has since been well investigated to increase our understanding on the mechanism and regulation on how cancer cells resist apoptosis. Further anti-apoptotic strategies targeting the BCL-2 proteins, the p53 genome, amongst other cell signals within apoptosis is well underway.
Apoptosis or ‘cell death’, is a normal biological self-destruct program that cells have. It is an ordered and orchestrated event that occurs in physiological and pathological conditions. When a cell detects that it has damaged DNA, apoptosis is activated to remove the cell from the body. Other apoptotic signals include signaling imbalance caused by cancer gene activation; lack of oxygen supply; or insufficient growth factors. In cancer, too little apoptosis occurs resulting in malignant cells that will not die.
The mechanism of apoptosis is complex and involves many pathways. The primary regulators of apoptosis are proteins belonging to the BCL-2 family that are either pro-apoptotic (trigger apoptosis) or anti-apoptotic (inhibit apoptosis). Apoptosis regulators also include death receptors on the cell surface that bind to death signaling molecules. Cells then need the ability to detect the necessary conditions for triggering apoptosis. The most common method cancer cells use to escape death is loss of the apoptosis gatekeeper, the protein p53. If repair is not possible then apoptosis is induced Letai et al (2017).
Following the landmark discovery of BCL2 in cancer nearly 3 decades ago, a break-through anti-cancer drug targeting BCL2 is discovered. The role of BCL2 in cancer cell’s evasion of apoptosis was identified in 1988 and in 2016 the BCL2 anti-cancer therapy Venetoclax was successfully identified in chronic lymphocytic leukemia.
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We at In Vitro Technologies are committed to groundbreaking cancer research to understand how cancer cells ‘resist apoptosis’ and improved therapeutic strategies. So we have brought together a range of quality resources to help you explore this hallmark. With our expert support, the solutions we offer guarantee high quality, reproducible results, allowing you to accelerate cancer discoveries.
Powerful tools are available to begin quality translational research elucidating ‘resistance to apoptosis’ in multiple cancers. The ATCC Cell Death Pathway BCL-2 Family Cell Line Panels together with the p53 Hotspot Mutation Tumor Cell Panels are composed of cell lines with mutations that have been verified and validated by molecular signature, mutational status and cancer type allowing you to begin your research workflow with authenticated, well-characterised cells.
The Cell Death Pathway BCL-2 Family Cell Line Panels 1 and 2 are useful for the study of cell apoptosis signalling pathways, BCL-2 family member molecular mechanisms, and mitochondrial dysfunction.
Find out more about BCL-2 Family Cell Line Panels
These ATCC Molecular Signature p53 Hotspot Mutation Cell Panels are cell-based research models with cell lines derived from tumors of various tissue origins that have been sequenced and validated for mutations in the p53 gene
Find out more about p53 Hotspot Mutation Cell Panels and ATCC Tumor Cell Panels
>R&D Systems Apoptosis and p53 Interactive Pathway highlight the factors involved in both the extrinsic or intrinsic pathway of caspase activation, allowing researchers the opportunity to identify the solutions available to explore the mechanisms of apoptosis evasion in cancer cells and the basis of therapeutic intervention.
The presentation of phosphatidylserine (PS) on the cell surface is a well-validated method of measuring apoptosis (Martin, S., et al. 1995). Until now, apoptosis measurements were end-point assays offering a snap shot of the process at a specific point. These assays work well when measuring multiple time points, but the nature of measuring multiple wells at multiple time points creates additional variability, and uses a large amount of sample and reagent to do so. This snap shot approach also increases the likelihood of missing data as the time points selected might not capture the events of interest.
If you are investigating the apoptotic Hallmarks of Cancer then Promega’s RealTime-Glo Annexin V apoptosis assay offers accurate, real time apoptosis detection, in an easy-to-use ‘add and measure’ format that minimises the amount of sample and reagent required.
The non-lytic reagent also offers researchers the opportunity to multiplex this assay with other measures of cell health and viability, to provide additional confirmation of apoptosis. The bioluminescent signal is sensitive and specific and is suitable for high throughput screening of cell lines or apoptosis inducing compounds in a 96 well plate format using a multi-mode plate reader.
