This product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A2780 human ovarian carcinoma cell line, with targeted disruption of the CASP8 gene. The polyclonal pool preserves genetic diversity, reducing clonal artifacts and providing a robust loss-of-function model for studies of caspase-8 biology.
The A2780 line is a widely used human ovarian carcinoma model derived from an untreated patient. It is an adherent epithelial line commonly employed in drug sensitivity, chemoresistance, and apoptosis research, offering a clinically relevant background for dissecting cell death pathways in ovarian cancer.
Caspase-8 is an initiator caspase that mediates extrinsic apoptosis, necroptosis, and inflammatory signaling. Upon death receptor ligation (e.g., Fas, TRAIL-R, TNF-R1) by ligands (FasL, TRAIL, TNF-??), caspase-8 is recruited by FADD to the DISC and activated. Active caspase-8 cleaves executioner caspases-3/7 and Bid, promoting apoptosis. It also regulates necroptosis by controlling RIPK1/RIPK3; its absence permits RIPK1/RIPK3-dependent phosphorylation of MLKL and necroptotic death. Additionally, caspase-8 interacts with c-FLIP, TRAF2, XIAP, and cIAP1/2 to modulate TLR signaling and inflammasome activity.
In A2780 ovarian carcinoma cells, loss of caspase-8 disrupts death receptor-mediated apoptosis, enabling studies of drug resistance and compensatory cell death mechanisms. Ovarian tumors frequently evade apoptosis through modulation of caspase-8 pathways; this knockout model thus recapitulates clinically relevant alterations. It is instrumental for probing how cancer cells balance apoptosis and necroptosis, and for screening compounds that re-sensitize cells to death ligands.
Typical applications include mechanistic analysis of extrinsic apoptosis and necroptosis, drug sensitivity profiling, and screening for caspase-8 modulators. Representative assays include Western blotting for caspase-8 and substrate cleavage, Annexin V apoptosis assays, caspase-8 activity measurements, co-immunoprecipitation with FADD, and death ligand (TRAIL/FasL) sensitivity testing. RT-qPCR can monitor transcriptional responses downstream of CASP8 disruption. These cells support research in ovarian cancer, cell death signaling, and therapeutic development. For additional technical information or to discuss custom CRISPR editing services, please contact Ascent Research.
