Comparison of Curcumin and Curcuminoids in terms of mechanisms of action and treatment efficiency in DIPG

Diffuse intrinsic pontine glioma (DIPG) is a pediatric high-grade glioma of the brainstem, characterized by a very poor prognosis. 85 % of DIPG carry a mutation in lysine 27 of histone 3 (H3K27M), leading to an epigenetic imbalance. Due to lack of efficient conventional treatment options parents of affected children often use therapeutic adjuvants such as Curcumin (Cur). To investigate the molecular and biological effect of Cur on DIPG cells in dependence of the H3K27M mutation isogenic cell lines were subjected to cell viability assays, immunoblotting, and RNA sequencing. In addition, to overcome the limited therapeutic use due to poor bioavailibility, we further compared Cur with synthesized Curcuminoids (CurO) in terms of their mechanisms of action. Our preliminary results showed that Cur and CurO similarly reduce cell viability in DIPG via induction of autophagy, independently of the underlying H3K27-status. However, both Cur and CurO modulate the H3K27M-induced epigenetic imbalance. In summary, Cur and CurO induce anti-tumor effects probably throughout similar processes. Thus, CurO with its improved bioavailability might serve as potent therapeutic adjuvant for DIPG in future.

Publikationsverlauf

Artikel online veröffentlicht:
13. Mai 2020