The CBR1 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the CBR1 gene, encoding NADPH-dependent carbonyl reductase 1. This product comprises a heterogeneous pool of HeLa cells carrying diverse CRISPR/Cas9-mediated gene disruptions at the CBR1 locus, providing a robust loss-of-function model for studying CBR1-dependent processes without the limitations of single-cell clonal selection.
The HeLa cell line is an immortalized human epithelial cell line derived from a HPV18-positive cervical adenocarcinoma. HeLa cells are extensively employed in biomedical research due to their robust growth characteristics and well-characterized genomic background, making them a versatile platform for investigating oncogenic signaling, drug metabolism, and cellular stress responses.
CBR1 encodes a cytosolic NADPH-dependent carbonyl reductase that catalyzes the reduction of a broad range of carbonyl substrates. The enzyme??s expression is transcriptionally regulated by nuclear factor erythroid 2-related factor 2 (Nrf2), aryl hydrocarbon receptor (AhR), and peroxisome proliferator-activated receptor gamma (PPAR??). Functionally, CBR1 is a critical node in the arachidonic acid cascade, acting downstream of prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2) to reduce prostaglandin E2 and prostaglandin F2?? into 15-hydroxyprostaglandins, which are further processed by aldo-keto reductase family 1 member C3 (AKR1C3) and hematopoietic prostaglandin D synthase (HPGDS). Additionally, CBR1 detoxifies anthracycline chemotherapeutics such as doxorubicin and daunorubicin by converting them to their corresponding alcohol metabolites through NADPH-dependent reduction, thereby diminishing their cytotoxic efficacy. This dual role places CBR1 at the intersection of prostaglandin metabolism and xenobiotic detoxification.
In the HeLa cellular context, CRISPR/Cas9-mediated knockout of CBR1 abolishes the reduction of prostaglandins and anthracyclines, leading to disrupted prostaglandin signaling and potentially enhanced sensitivity to chemotherapeutic agents. The HPV18-positive cervical adenocarcinoma origin of HeLa cells provides a clinically relevant backdrop for examining how carbonyl reductase activity influences drug resistance and inflammatory pathways in epithelial malignancies. This knockout model thus enables the dissection of CBR1’s contributions to cellular detoxification programs and the modulation of pro-inflammatory lipid mediators.
Researchers can employ this polyclonal knockout population to investigate mechanisms of chemotherapy drug resistance, utilizing MTT or colony formation assays to assess cell viability following anthracycline treatment. For prostaglandin signaling studies, quantification of 15-hydroxyprostaglandins and related metabolites by LC-MS/MS, combined with western blotting and RT-qPCR to profile pathway components, offers a comprehensive analytical approach. Immunofluorescence can be used to visualize changes in downstream effector localization. For further details and technical support, please contact Ascent Research.
