The IDH2 knockout SK-HEP-1 polyclonal cells constitute a CRISPR/Cas9-edited polyclonal cell population featuring targeted disruption of the IDH2 gene in a human hepatocellular carcinoma background. This product provides a loss-of-function model system for the mitochondrial isocitrate dehydrogenase 2 (IDH2) enzyme, enabling researchers to dissect the roles of IDH2-catalyzed metabolic reactions in liver cancer biology. The polyclonal nature of the knockout population preserves heterogeneous genetic editing events across the cell pool, allowing robust functional studies without the clonal selection artifacts that can arise in single-cell-derived lines.
The host cell line, SK-HEP-1, is a widely utilized human hepatocellular carcinoma cell line originally isolated from the ascitic fluid of a patient with adenocarcinoma of the liver. SK-HEP-1 cells exhibit an epithelial morphology and serve as a well-characterized in vitro model for hepatic tumorigenesis, retaining key molecular features relevant to hepatocellular carcinoma research. The genetic background of this cell line supports investigations into liver cancer metabolism, drug response, and oncogenic signaling pathways.
IDH2 encodes a mitochondrial NADP+-dependent isocitrate dehydrogenase that catalyzes the oxidative decarboxylation of isocitrate to ??-ketoglutarate (??-KG), concomitantly generating NADPH. This reaction is integral to the citric acid cycle and to cellular redox homeostasis. IDH2 function is regulated upstream by factors such as FOXO3a, NRF2, SIRT3, and HIF-1??, and its activity directly influences ??-KG-dependent dioxygenases, including TET2, KDM histone demethylases (e.g., KDM4A), and prolyl hydroxylases. By forming a homodimer and interacting with mitochondrial chaperones HSP60 and HSP10, IDH2 governs NADPH/NADP+ ratios and ??-KG availability, thereby modulating DNA and histone methylation patterns, lipid biosynthesis, and redox signaling. Knockout of IDH2 consequently depletes mitochondrial NADPH pools, reduces ??-KG levels, and impairs the function of these dioxygenases, leading to altered epigenetic landscapes and heightened sensitivity to oxidative stress.
In the SK-HEP-1 hepatocellular carcinoma context, IDH2 disruption provides a powerful tool to study how loss of mitochondrial NADPH production impacts liver cancer cell fitness. Although IDH2 mutations are uncommon in hepatocellular carcinoma, the enzyme??s role in managing oxidative stress and sustaining biosynthetic processes is critical for cancer cell survival. This knockout model allows researchers to probe metabolic vulnerabilities specific to liver cancer cells, potentially revealing synthetic lethal interactions or sensitization to inhibitors targeting glutamine metabolism or redox pathways. The polyclonal format further enables assessment of heterogeneous cellular responses to IDH2 loss within a tumor cell population.
This IDH2 knockout SK-HEP-1 polyclonal cell product is suited for a wide range of advanced research applications, including cancer metabolism, redox biology, and epigenetic regulation. Investigators can employ assays such as NADPH/NADP+ ratio measurements, ??-ketoglutarate quantification, ROS detection, metabolic flux analysis, and DNA methylation profiling to characterize the functional consequences of IDH2 disruption. The model also supports drug sensitivity screening against agents that perturb redox balance or glutamine utilization, as well as TET2 activity assays to examine dioxygenase-dependent epigenetic changes. For further technical specifications and ordering information, please contact Ascent Research.
