The CBS Knockout A2780 polyclonal cells are a genetically engineered human cell population derived from the A2780 ovarian carcinoma line, featuring CRISPR/Cas9-mediated disruption of the cystathionine beta-synthase (CBS) gene. This polyclonal knockout population enables loss-of-function analysis of CBS without the biases of single-cell cloning, preserving the heterogeneity of the parental line. The product serves as a robust tool for studying transsulfuration pathway dynamics and homocysteine metabolism in an epithelial ovarian cancer context.
The A2780 cell line was established from an untreated patient with ovarian carcinoma and has become a cornerstone model in cancer biology and preclinical drug evaluation. These epithelial cells display characteristics relevant to high-grade serous ovarian cancer, including sensitivity to platinum-based chemotherapeutics and reproducible growth kinetics. The A2780 background provides a clinically pertinent platform for examining how metabolic alterations influence tumor cell fitness, therapy response, and redox balance.
CBS is a heme- and pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the condensation of homocysteine and serine to form cystathionine, the rate-limiting step of the transsulfuration pathway. Its activity is allosterically stimulated by S-adenosylmethionine and modulated by cellular redox state, hypoxia, and vitamin B6 availability. Downstream, cystathionine is converted to cysteine, the precursor for glutathione, the major intracellular antioxidant. By controlling homocysteine clearance and cysteine supply, CBS integrates one-carbon metabolism with redox homeostasis and antioxidant defense.
In A2780 cells, CBS knockout disrupts this regulatory node, causing accumulation of homocysteine and depletion of cysteine and glutathione pools. This metabolic shift impairs the cell??s ability to counteract oxidative stress and may enhance vulnerability to reactive oxygen species (ROS)-inducing agents. Given the role of glutathione in detoxifying chemotherapeutics and modulating apoptotic thresholds, CBS deficiency can influence drug sensitivity, particularly to cisplatin and other stressors that elevate oxidative load.
Researchers can apply this model to dissect the metabolic dependencies of ovarian cancer, including the contribution of transsulfuration to redox regulation, drug resistance, and proliferation. Validated applications include western blotting and RT-qPCR for CBS expression, quantitative assays for homocysteine, cysteine, and glutathione levels, cell viability assays under oxidative challenge (e.g., H?O? treatment), apoptosis profiling, and cisplatin sensitivity testing. Broad metabolite profiling can further elucidate pathway flux alterations. For additional information or technical support, please contact Ascent Research.
