The BDH1 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the BDH1 gene in HCT 116 human colorectal carcinoma cells. This polyclonal pool contains diverse loss-of-function alleles, enabling robust functional studies without clonal bias. The product provides a ready-to-use tool for investigating BDH1-dependent metabolic processes in a cancer-relevant context.
The HCT 116 cell line originates from colorectal adenocarcinoma and harbors KRAS G13D and CTNNB1 mutations, along with MSI-H status and a near-diploid genome. These genetic features render cells dependent on metabolic adaptations, making HCT 116 a well-established model for cancer metabolism studies. Its colorectal origin situates this knockout model within gastrointestinal cancer research, where ketone body utilization may influence tumor metabolic plasticity.
BDH1 encodes a mitochondrial enzyme catalyzing NAD+-dependent oxidation of (R)-3-hydroxybutyrate to acetoacetate, a key step in ketone body utilization. It operates within a pathway including HMGCS2, HMGCL, OXCT1, and ACAT1. Transcriptionally regulated by PPAR??, PGC-1??, and FOXOs, BDH1 is activated by AMPK, insulin, and glucose deprivation signals. It interacts with OXCT1, ACAT1, and respiratory chain complexes to generate acetyl-CoA, driving ATP production and histone acetylation. Disruption impairs ketone body oxidation and mitochondrial bioenergetics.
In HCT 116 cells, BDH1 knockout creates a model to probe ketone body-dependent energy metabolism in colorectal cancer. The tumor??s reliance on metabolic flexibility under nutrient stress suggests that loss of BDH1 may compromise ketone body utilization, sensitizing cells to metabolic challenges. This model enables dissection of oncogenic KRAS and CTNNB1 pathway interactions with mitochondrial ketone oxidation, offering a platform to identify synthetic lethal vulnerabilities and metabolic dependencies. The polyclonal format avoids clonal artifacts, representing a heterogeneous knockout population.
Applications include dissecting ketone body metabolism in colorectal cancer, screening for synthetic lethal interactions under nutrient-depleted conditions, and evaluating responses to metabolic inhibitors. Functional analysis can be performed using Seahorse mitochondrial respiration assays, ATP quantification, western blotting, RT-qPCR, BDH1 enzyme activity assays, colony formation, and metabolomic profiling. For further information, please contact Ascent Research.
