Identification of new therapeutic targets and natural compounds against diffuse intrinsic pontine glioma (DIPG).

Identification of new therapeutic targets and natural compounds against diffuse intrinsic pontine glioma (DIPG). Bioorg Chem. 2020 Apr 13;99:103847 Authors: Chen J, Lin Z, Barrett L, Dai L, Qin Z Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor which accounts for about 10-20% of childhood brain tumors. The survival rate for DIPG remains very poor, with a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of a large number of clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care for DIPG. In the current study, we screened a natural product library and for the first time identified 6 natural compounds displaying inhibitory effects on DIPG proliferation and anchorage-independent growth through inducing tumor cell apoptosis and cell cycle arrest. Subsequent RNA-Sequencing and functional validation revealed the molecular mechanisms of these compounds with anti-DIPG activities, and identified new cellular factors such as Fibronectin 1 (FN1) and Eukaryotic translation initiation factor 3 subunit C-like (EIF3CL), required for DIPG survival as potential therapeutic targets. Our study provides promising directions to fight against this deadly pediatric cancer. PMID: 32311581 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research