The CASP9 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the CASP9 gene in the Ca Ski human cervical carcinoma line. This loss-of-function model eliminates caspase-9, the initiator caspase of intrinsic apoptosis, enabling robust studies of mitochondrial cell death signaling.
The Ca Ski host cells are an HPV16-positive cervical epidermoid carcinoma line established from a mesenteric metastasis. Widely used as a cervical cancer model, they provide a disease-relevant background to assess apoptosis regulation and chemotherapeutic response.
Caspase-9 is activated within the apoptosome, a complex formed by cytochrome c and APAF1 upon mitochondrial outer membrane permeabilization. Active caspase-9 cleaves executioner caspases-3 and -7, which then cleave substrates such as PARP to execute apoptosis. Caspase-9 activity is regulated by XIAP, SMAC/DIABLO, BCL-2 family proteins (BAX, BAK, BCL-2), and survival kinases (AKT, ERK). Interacting cofactors include Hsp70, Hsp90, and PHAP.
In the context of HPV16-driven cervical carcinoma, CASP9 knockout confers resistance to mitochondrial apoptosis, uncoupling cytochrome c release from caspase activation. This model allows dissection of caspase-9-dependent death pathways and exploration of apoptosis evasion mechanisms relevant to HPV oncogenesis and chemoresistance.
Applications include apoptosis resistance profiling, drug sensitivity screening against agents like cisplatin and staurosporine, and identification of caspase-independent cell death. Assays such as Annexin V/PI flow cytometry, caspase-3/7 activity measurement, western blotting for cleaved caspase-3/PARP, JC-1 mitochondrial membrane potential assay, and MTT viability testing are well-suited. For further information, contact Ascent Research.
