Inhibition of dihydroorotate dehydrogenase by doxorubicin and brequinar sensitize cancer cells to TRAIL-induced apoptosis

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent in selectively killing tumor cells. However, TRAIL monotherapy is not especially successful due to the fact that many cancer cells are resistant to TRAIL. Chemotherapeutic agents, such as doxorubicin have been shown to act synergistically with TRAIL on cancer cells, but the exact mechanisms of actions are poorly understood. In this study we performed high-throughput siRNA screening and genome-wide gene expression profiling on doxorubicin treated U1690 cells to explore novel mechanisms underlying doxorubicin-TRAIL synergy. The screening and expression profiling results were integrated and dihydroorotate dehydrogenase (DHODH) was identified to be a potential candidate. DHODH is rate-limiting enzyme in the py

ORGANISM(S): Homo sapiens

SUBMITTER: He Tao 

PROVIDER: S-ECPF-GEOD-42531 | biostudies-other |

REPOSITORIES: biostudies-other