The ACOD1 Knockout SK-OV-3 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-OV-3 human ovarian adenocarcinoma epithelial cell line, engineered for loss-of-function studies of the ACOD1 gene (also known as IRG1). This polyclonal knockout population, generated through CRISPR/Cas9-mediated gene disruption, provides a heterogeneous mix of edited cells suitable for investigating the role of aconitate decarboxylase 1 in cancer immunometabolism and inflammation without the need for single-cell cloning. As a polyclonal format, it retains a range of genetic backgrounds while targeting the locus of interest, enabling robust population-level analyses.
The SK-OV-3 host cell line was originally established from the ascites of a patient with ovarian adenocarcinoma and is widely employed as a model for high-grade serous ovarian cancer. SK-OV-3 cells harbor TP53 and PIK3CA mutations, characteristic of aggressive disease, and are commonly used to study ovarian cancer biology, drug response, and metastatic mechanisms. The epithelial morphology and tumorigenic properties of SK-OV-3 make it a relevant system for examining molecular pathways that influence tumor progression and therapeutic resistance.
ACOD1 encodes IRG1, the enzyme responsible for catalyzing the production of itaconate from cis-aconitate in the tricarboxylic acid (TCA) cycle. Itaconate exerts anti-inflammatory and antioxidant effects by activating the transcription factor NRF2 through KEAP1 alkylation, inhibiting succinate dehydrogenase (SDH) to modulate mitochondrial respiration, and reducing reactive oxygen species (ROS) levels. ACOD1 expression is upregulated by pro-inflammatory stimuli including TLR ligands such as LPS, interferon-gamma (IFNG), and tumor necrosis factor (TNF), acting downstream of NF-??B and AP-1 transcription factors. IRG1-derived itaconate feeds back to suppress inflammation by downregulating NLRP3 inflammasome components and I??B??, and by promoting ATF3-dependent anti-inflammatory gene expression. Additionally, itaconate can influence glycolysis-related genes and interact with HIF1A, linking metabolic reprogramming to immune responses.
In the context of ovarian cancer, ACOD1 may regulate the inflammatory tumor microenvironment and metabolic adaptations of cancer cells. SK-OV-3 cells, with their defined oncogenic mutations, offer a platform to dissect how loss of endogenous itaconate production affects cell-intrinsic inflammatory signaling, ROS management, and interactions with immune cells. This knockout model is particularly valuable for exploring the function of the KEAP1-NRF2-SDH axis and toll-like receptor signaling cascades in cancer cells, as well as the impact on upstream regulators such as TLR4, MYD88, and IRF3, and downstream targets like ATF3 and HIF1A.
Researchers can apply this ACOD1 polyclonal knockout cell population to a variety of experimental approaches, including immunometabolism studies in cancer, investigation of itaconate’s role in the tumor microenvironment, and analysis of anti-inflammatory mechanisms within ovarian cancer cells. Typical assays involve Western blotting for ACOD1 protein, RT-qPCR for ACOD1 mRNA, ELISA for itaconate quantification, NF-??B reporter assays to assess inflammatory signaling, ROS detection, and metabolic flux analysis to evaluate TCA cycle and glycolytic activity. These tools enable phenotypic characterization of the knockout and screening of metabolic or anti-inflammatory compounds. For additional information or technical support, please contact Ascent Research.
