The AIFM2 Knockout NCI-H1703 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1703 human lung adenocarcinoma cell line. This loss-of-function model is engineered to disrupt the AIFM2 gene, which encodes a mitochondrial flavoprotein oxidoreductase involved in programmed cell death regulation. The polyclonal pool provides a genetically diverse population of cells carrying targeted gene disruption, suitable for functional studies of AIFM2 without clonal selection.
The host NCI-H1703 cell line is an epithelial model originating from a primary lung adenocarcinoma in a 54-year-old male smoker. It retains key features of non-small cell lung cancer and is frequently used to study tumor biology, drug responses, and oncogenic signaling. Its application as a host for CRISPR knockout enables direct dissection of gene function in a lung adenocarcinoma context.
AIFM2 is a mitochondrial flavoprotein that suppresses ferroptosis by reducing CoQ10 to ubiquinol, a potent lipophilic antioxidant that halts lipid peroxidation. During apoptosis, AIFM2 translocates to the nucleus, where it interacts with DNA to drive chromatin condensation and caspase-independent DNA fragmentation. AIFM2 activity is regulated by upstream factors including p53, KEAP1/NRF2, and GPX4, and interfaces with the ferroptosis machinery via ACSL4 and SLC7A11, as well as apoptotic mediators such as BAX and caspase-3. Disruption of AIFM2 therefore uncouples these intersecting pathways, providing a tool to study cell death network dynamics.
Knockout of AIFM2 in NCI-H1703 cells disrupts the dual control over ferroptosis and apoptosis, rendering the cells more susceptible to ferroptosis inducers like Erastin and RSL3. This sensitized state arises from compromised CoQ10 antioxidant defense, leading to elevated lipid reactive oxygen species. The model thus allows exploration of AIFM2’s role in lung adenocarcinoma cell death evasion and its potential as a therapeutic vulnerability for ferroptosis-dependent tumor suppression.
Research applications include mechanistic studies of ferroptosis in lung cancer, high-throughput screening of ferroptosis-inducing compounds, and interrogation of apoptosis signaling. Assays such as cell viability measurements, lipid peroxidation quantification using C11-BODIPY, Annexin V/PI apoptosis detection, Western blotting, RT-qPCR, and immunofluorescence are routinely used with this product. For additional technical information, please contact Ascent Research.
