RESUMO
Oral tongue squamous cell carcinoma (OTSCC) was one of the most hypoxic tumors with unfavorable outcomes. Hypoxia-inducible factor-1 (HIF-1) signaling was associated with cancer proliferation, lymph node metastasis, angiogenesis and poor prognosis of OTSCC. Dihydroorotate dehydrogenase (DHODH) catalyzed the rate-limiting step in the de novo pyrimidine biosynthesis. The aim of the study was to explore the biological function of DHODH and investigate whether DHODH regulated HIF-1 signaling in OTSCC. Proliferation, migration and anoikis resistance were used to determine the function of DHODH. Western blot and luciferase activity assays were used to determine the regulatory role of DHODH on HIF-1. We found that increased DHODH expression was associated with advanced tumor stage and poorly differentiated tumor in head and neck cancer patients in The Cancer Genome Atlas (TCGA). DHODH enhanced the proliferation and aggressiveness of OTSCC. Moreover, DHODH prompted tumor growth and metastasis in vivo. DHODH promoted transcription, protein stability, and transactivation activity of HIF1A. DHODH-induced HIF1A upregulation in OTSCC can be reversed by reactive oxygen species (ROS) scavenger, indicating that DHODH enhanced HIF1A expression via ROS production. DHODH inhibitor suppressed DHODH-mediated ROS generation and HIF1A upregulation. Targeting DHODH using clinically available inhibitor, atovaquone, might provide a new strategy to treat OTSCC.
RESUMO
A cascade three-component iodoazidation of para-quinone methides to construct spiro[4.5]deca-6,9-dien-8-ones under mild conditions has been developed. The chemoselective 1,6-addition of azide radical triggered a regioselective 5-exo-dig cyclization/radical coupling sequence, enabling C-N, C-C, and C-I bond formations in a one-pot procedure with high efficiency.
RESUMO
The histones including H2a, H2b, H3 and H4 purified from pig liver tissue were immobilized onto Sepharose 4B to create a histone-Sepharose column. During chromatography of cow milk casein by histone-Sepharose column, two isoforms of prion protein (PrP(c)) with 34 and 30kDa molecular mass corresponding to diglycosylated and monoglycosylated PrP(c) respectively were found to be captured by histone ligands. To further verify the interaction between histones and PrP(c), the PrP(c)-Sepharose column was prepared and used to separate the histones. Two chromatography processes and SDS-PAGE demonstrated that only H3 in the histones was found to interact with PrP(c). This study suggested H3 could be the target molecule of PrP(C) in nuclei, which might be useful for understanding the prion disease.
