TY - JOUR
AR - COR-2020-7-113
TI - Apoptosis Cellular Models in Cancer Therapeutics
AU - Chien-An, Andy Hu
AU - Warren , Laskey
AU - Shulin , Fu
AU - Yinsheng , Qiu
AU - Yulan , Liu
AU - Xueqin , Ding
AU - Yulong , Yin
AU - Thomas , Ma
AU - Hitendra , Chand
AU - Larry , Sklar
JO - Clinical Oncology and Research
PY - 2020
DA - Tue 21, Jul 2020
SN - 2613-4942
DO - http://dx.doi.org/10.31487/j.COR.2020.07.13
UR - https://www.sciencerepository.org/apoptosis-cellular-models-in-cancer-therapeutics_COR-2020-7-113 
KW - ApoL6, apoptosis, autophagy, atherosclerosis, cancer, drug screening, high throughput
AB - 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.