Genome-Scale Modeling of NADPH-Driven β-Lapachone Sensitization in Head and Neck Squamous Cell Carcinoma.

ABSTRACT:

Aims

The purpose of this study was to investigate differential nicotinamide adenine dinucleotide phosphate, reduced (NADPH) production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β-lapachone.

Results

We have developed a novel human genome-scale metabolic modeling platform that combines transcriptomic, kinetic, thermodynamic, and metabolite concentration data. Upon incorporation of this information into cell line-specific models, we observed that the radiation-resistant HNSCC model redistributed flux through several major NADPH-producing reactions. Upon RNA interference of canonical NADPH-producing genes, the metabolic network can further

SUBMITTER: Lewis JE 

PROVIDER: S-EPMC6104251 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature