The CBR1 Knockout HT29 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HT29 human colorectal adenocarcinoma line, engineered for targeted disruption of the CBR1 gene. This polyclonal population provides a loss-of-function model for studying carbonyl reductase 1 (CBR1) in an intestinal epithelial context, without clonal isolation.
HT29 cells, established from a 44-year-old Caucasian female, are a widely used model of colorectal adenocarcinoma with epithelial barrier function, glandular secretion, and active drug metabolism pathways. They retain expression of phase I and II metabolizing enzymes, making them suitable for ADME-Tox investigations and cancer pharmacology.
CBR1 encodes an NADPH-dependent monomeric carbonyl reductase that reduces endogenous substrates such as prostaglandin E2 and exogenous xenobiotics including doxorubicin. CBR1 is transcriptionally activated by NFE2L2 (Nrf2) and AHR in response to oxidative stress and electrophiles, and functions downstream of PTGS2 and PTGES in prostaglandin metabolism. Its activity converts doxorubicin to the cardiotoxic metabolite doxorubicinol and detoxifies lipid peroxidation products like 4-hydroxy-2-nonenal, linking CBR1 to both chemoresistance and cellular antioxidant defenses.
In the HT29 background, CBR1 knockout abolishes NADPH-dependent carbonyl reduction, leading to impaired prostaglandin inactivation and accumulation of reactive aldehydes. This sensitizes cells to doxorubicin cytotoxicity by preventing metabolic detoxification, and compromises protection against oxidative stress, making this polyclonal knockout model valuable for dissecting CBR1-mediated contributions to drug resistance and redox homeostasis in colorectal cancer.
Researchers can employ this polyclonal knockout population in a variety of functional assays, including MTT-based cytotoxicity testing with doxorubicin, LC-MS quantification of doxorubicinol formation, prostaglandin conversion assays, TBARS for lipid peroxidation, DCFDA-based ROS detection, and apoptosis flow cytometry. It supports studies on Nrf2/ARE signaling, chemopreventive agent efficacy, and metabolic profiling in intestinal epithelial cells. For additional product information or to inquire about custom cell engineering solutions, please contact Ascent Research.
