The CBR3 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A-549 human lung adenocarcinoma cell line. This product features disruption of the CBR3 gene using CRISPR/Cas9-mediated gene targeting, yielding a mixed population that serves as a loss-of-function model without the clonal selection biases inherent to monoclonal lines.
The parental A-549 cell line originates from lung adenocarcinoma tissue of a 58-year-old male and displays alveolar Type II epithelial characteristics. Widely used as an in vitro model for human lung cancer, these cells retain relevant expression of metabolic enzymes and transcription factors, making them suitable for studies of carbonyl metabolism and drug resistance mechanisms.
CBR3 encodes an NADPH-dependent carbonyl reductase that catalyzes the reduction of endogenous prostaglandin E2 to 15-keto-PGF2?? and the chemotherapeutic doxorubicin to doxorubicinol. Transcriptional regulation occurs through NFE2L2 (Nrf2) in response to oxidative stress and PPARgamma agonists, integrating with cellular redox homeostasis and xenobiotic response pathways. The enzyme utilizes NADPH as a cofactor and may interact with other short-chain dehydrogenases. Downstream, CBR3 activity lowers reactive carbonyl species and prostaglandin levels, influencing drug detoxification and contributing to anthracycline resistance.
In the A-549 lung adenocarcinoma context, disruption of CBR3 allows for rigorous investigation of carbonyl metabolism in cancer cell biology. This knockout model is especially valuable for dissecting anthracycline resistance, as CBR3-mediated doxorubicin metabolism reduces drug efficacy. Removing CBR3 function enables direct assessment of doxorubicin sensitivity, accumulation of carbonyl stress, and modulation of prostaglandin E2 signaling within a lung cancer-relevant cellular environment.
Intended applications include mechanistic studies of xenobiotic detoxification, carbonyl reductase roles in cancer metabolism, and modulators of anthracycline efficacy. Experimental approaches for characterization include western blotting and RT-qPCR to confirm CBR3 disruption, cell viability assays with doxorubicin to gauge drug sensitivity, carbonyl reductase activity and NADPH consumption assays, and LC-MS analysis of doxorubicin/doxorubicinol levels. Prostaglandin E2 quantification and apoptosis assays (caspase-3/7) further define the knockout phenotype. Researchers can contact Ascent Research for additional technical information.
