The ACOD1 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human NCI-H1703 lung squamous cell carcinoma cell line, with targeted disruption of the ACOD1 gene (encoding aconitate decarboxylase 1, also known as IRG1). This product provides a heterogeneous pool of cells carrying loss-of-function mutations, enabling studies of itaconate production and immunometabolic regulation without clonal selection.
NCI-H1703 is a non-small cell lung cancer (NSCLC) cell line of squamous cell carcinoma origin, established from a 54-year-old male patient. These adherent epithelial cells are widely used in lung cancer research, including investigations of tumor biology, drug sensitivity, and microenvironmental interactions. Their genetic background makes them a relevant model for squamous cell carcinoma.
ACOD1 encodes IRG1, which decarboxylates cis-aconitate to produce itaconate, a metabolite with anti-inflammatory and immunomodulatory functions. Itaconate alkylates KEAP1 to activate NRF2 and inhibits succinate dehydrogenase (SDH), reducing mitochondrial ROS and pro-inflammatory cytokines. ACOD1 expression is induced by LPS/TLR4 signaling, type I interferons via JAK-STAT, and cytokines like TNF-?? and IL-1??. Downstream, itaconate suppresses NLRP3 inflammasome and alters glycolysis. Key interacting factors include KEAP1, SDH, IRF1, and ATF3, linking ACOD1 to NF-??B signaling, redox control, and TCA cycle modulation.
In NCI-H1703 cells, ACOD1 knockout eliminates itaconate synthesis, likely enhancing inflammatory responses and altering metabolic profiles. This disruption can reveal roles of ACOD1 in regulating NRF2/KEAP1 antioxidant responses and NF-??B signaling, affecting cell proliferation, cytokine output, and oxidative stress sensitivity. As lung squamous cell carcinomas often exhibit dysregulated immunometabolism, this model helps dissect how itaconate influences cancer cell fitness and immune microenvironment interactions.
Applications include immunometabolism research, inflammation studies, and cancer cell metabolism. Representative assays comprise LC-MS for itaconate quantification, RT-qPCR for ACOD1 and cytokine expression, Western blot for NRF2, KEAP1, and SDH, Seahorse metabolic flux analysis, and ELISA for cytokine profiling. The polyclonal knockout population is suitable for drug screening targeting anti-inflammatory pathways and for investigating tumor microenvironment dynamics. For further information, please contact Ascent Research.
