IDH2 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from NCI-H1703 human lung squamous cell carcinoma cells. This product features targeted disruption of the IDH2 gene via CRISPR/Cas9, resulting in a loss-of-function model of mitochondrial isocitrate dehydrogenase 2. The polyclonal format provides a genetically heterogeneous knockout pool, enabling robust functional studies while minimizing clonal selection artifacts. These cells serve as a versatile tool for dissecting wild-type IDH2 functions in cancer metabolism and redox biology.
The host cell line NCI-H1703 is a lung squamous cell carcinoma model originally established from a 54-year-old male patient. This adherent epithelial line recapitulates key features of squamous cell carcinoma of the lung, a subtype with limited targeted therapy options. NCI-H1703 cells harbor genomic alterations typical of lung squamous cell carcinoma and are widely employed in preclinical oncology research to study tumor metabolism, drug responses, and signaling pathways relevant to this aggressive cancer type.
IDH2 encodes mitochondrial NADP+-dependent isocitrate dehydrogenase, which converts isocitrate to ??-ketoglutarate while producing NADPH. Its activity is regulated by SIRT3-mediated deacetylation, AMPK phosphorylation, and transcriptional control by NRF2 and HIF1A under nutrient and redox stress. In the TCA cycle, IDH2 cooperates with citrate synthase, aconitase, and MDH2, and its product ??-ketoglutarate is an obligate co-substrate for TET2 and JmjC histone demethylases, coupling metabolism to epigenetic regulation. NADPH generated by IDH2 sustains glutathione-dependent antioxidant defenses and supplies reducing equivalents for ACLY-mediated lipogenesis. Disruption of IDH2 by CRISPR/Cas9 halts this canonical activity, causing diminished ??-ketoglutarate and NADPH, thereby impairing dioxygenase function and redox homeostasis.
In NCI-H1703 lung squamous cell carcinoma, IDH2 knockout creates a metabolic model to probe vulnerabilities from loss of wild-type IDH2. Although IDH2 mutations are rare in lung cancer, its activity supports redox balance and anabolism. Eliminating IDH2 exposes reliance on alternative NADPH pathways such as the pentose phosphate pathway or IDH1, sensitizing cells to oxidative stress and enabling synthetic lethal screening.
Applications include Seahorse metabolic flux analysis, NADP+/NADPH ratio assays, ??-ketoglutarate quantification, ROS detection by flow cytometry, colony formation under stress, and global metabolomic or transcriptomic profiling. This model is ideal for studying IDH2-dependent TET2 and histone methylation, identifying synthetic lethal interactions, and exploring metabolic vulnerabilities in lung squamous carcinoma. For further details, please contact Ascent Research.
