The CASP6 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human non-small cell lung carcinoma (NSCLC) cell line NCI-H1299. This product enables investigation of CASP6, an executioner caspase in apoptosis, through CRISPR/Cas9-mediated gene disruption, providing a heterogeneous polyclonal pool for bulk assays.
The parental NCI-H1299 cell line originates from a lymph node metastasis of lung adenocarcinoma, harboring a TP53 null genotype with wild-type KRAS and EGFR. Its p53-deficient background makes it a key model for p53-independent apoptosis and drug sensitivity studies, widely used in NSCLC research.
CASP6 is an executioner caspase activated by CASP8, CASP9, CASP3, and Granzyme B. Its primary substrates include lamin A (LMNA), lamin B1, PARP1, ACIN1, and HTT, whose cleavage drives chromatin condensation and apoptotic body formation. Endogenous inhibitors XIAP and BIRC5 regulate CASP6 activity, while upstream activators include FASLG/FAS and the apoptosome components Cytochrome c, APAF1, and CASP9. Thus, CASP6 integrates signals from both intrinsic and extrinsic apoptotic pathways.
In NCI-H1299 cells lacking TP53, CASP6 knockout impairs apoptosis execution and may confer chemoresistance, offering a model to study p53-independent cell death mechanisms. This tool is especially relevant for lung adenocarcinoma research, where apoptotic evasion contributes to tumor survival. Combined TP53 null and CASP6 deficiency can help identify synthetic lethal targets or agents that restore apoptotic sensitivity.
Applications include apoptosis resistance profiling, drug sensitivity assays (staurosporine, cisplatin), and neurodegeneration pathway analysis. Typical readouts encompass Western blotting (CASP6, cleaved lamin A), flow cytometry (Annexin V/PI), caspase activity assays, and MTT viability tests. The polyclonal format supports pooled screens and bulk functional genomics. For additional information, contact Ascent Research.
