Apoptosis Cellular Models in Cancer Therapeutics

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Apoptosis, one of the major regulated cell death pathways, is a highly regulated suicide mechanism used for the elimination of damaged and unwanted cells in multicellular organisms. Derailed apoptosis has been observed in two extremes of the disease spectrum, for example, cancer (too little apoptosis) and acute myocardial infarction (AMI; too much apoptosis). Using human cellular models and patient samples, we have previously shown that human apolipoprotein L6 (ApoL6), when overexpressed intracellularly, induces mitochondria- and reactive oxygen species (ROS)-mediated apoptosis. ApoL6 also blocks Beclin 1-initiated autophagy in both human colorectal cancer cells (DLD-1) and atherosclerotic lesion-derived cells. We speculated that small compounds enhancing ApoL6-induced apoptosis are candidate drugs to treat cancer. In the present study, we use our established human cellular models, high throughput and targeted screening strategies, and well-defined assays to identify nifedipine, L-proline, L-tryptophan, and picolinic acid as antiapoptotic agents, which would be candidate drugs for treating diseases such as AMI. We also identified fulvestrant and L-lysine, two compounds that can further enhance ApoL6-induced apoptosis in cancer cells.

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