The IDH2 Knockout SK-OV-3 Polyclonal Cells product consists of a polyclonal population of human SK-OV-3 ovarian adenocarcinoma epithelial cells in which the IDH2 gene has been disrupted via CRISPR/Cas9-mediated genome editing. This gene-edited polyclonal pool provides a heterogeneous loss-of-function model for studying isocitrate dehydrogenase 2 (IDH2) in the context of ovarian cancer biology. The polyclonal format preserves the diversity of editing outcomes across the cell population, enabling functional interrogation of IDH2 without clonal selection artifacts.
SK-OV-3 cells were originally derived from the ascites of a patient with ovarian adenocarcinoma and have since been widely employed as an epithelial model for ovarian cancer research. This cell line is particularly valued for investigations into tumorigenesis, metastatic dissemination, and mechanisms of drug resistance. The adherent, epithelial morphology of SK-OV-3 cells reflects the properties of malignant ovarian tumor cells, making them a relevant host for studying metabolic dependencies and oncogenic signaling pathways within ovarian cancer.
IDH2 encodes a mitochondrial enzyme that catalyzes the oxidative decarboxylation of isocitrate to ??-ketoglutarate (??-KG) while generating NADPH from NADP+. As a key component of the tricarboxylic acid (TCA) cycle, IDH2 contributes to NADPH regeneration, reductive carboxylation, and 2-oxoglutarate metabolism. Its activity is regulated by upstream factors such as HIF-1??, c-Myc, SIRT3, and cellular oxidative stress. IDH2 functions as a homodimer and interacts with TCA cycle enzymes, mitochondrial chaperones, and NADP+. Downstream, ??-KG and NADPH produced by IDH2 serve as critical substrates for TET2-mediated DNA demethylation, histone demethylases, NRF2-driven antioxidant responses, and lipid biosynthesis. Disruption of IDH2 therefore impacts both metabolic flux and epigenetic regulation.
In ovarian cancer cells, IDH2 plays a pivotal role in maintaining redox homeostasis and supporting anabolic metabolism, which are often dysregulated in tumor cells. The SK-OV-3 knockout model allows researchers to dissect how loss of IDH2 alters the balance between oxidative and reductive TCA cycle flux, sensitizes cells to oxidative stress, and disrupts ??-KG-dependent dioxygenases involved in DNA and histone modification. These alterations can potentially affect gene expression programs linked to proliferation, survival, and chemoresistance, underscoring the relevance of IDH2 as a metabolic vulnerability in ovarian cancer.
Applications of these IDH2 knockout polyclonal cells span a range of metabolic and epigenetic investigations typical in ovarian cancer research. Common assays include measurement of intracellular ??-KG levels, NADPH/NADP+ ratio determination, cell viability under hydrogen peroxide-induced oxidative stress, and colony formation or migration assays to assess phenotypic changes. Transcriptomic profiling via RNA-seq and ChIP-qPCR for histone marks such as H3K4me3 can reveal downstream transcriptional and epigenetic consequences, while metabolic flux analysis provides direct insight into TCA cycle alterations. These cells are also suitable for drug screening aimed at exploiting NADPH deficiency or for identifying synthetic lethal partners of IDH2 loss. For detailed product inquiries, please contact Ascent Research.
