Fig. 2
From: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy
Notch signaling pathway. Ligand from the presenting cell binds to the notch receptor on the receiving cell. Notch extracellular truncated (NEXT) domain is cleaved by ADAM metalloprotease and γ-secretase yielding the notch intracellular domain (NICD). NICD is translocated to the nucleus where it complexes with transcription factor CSL 9 CBF1/suppressor of hairless/Lag 1 and transcriptional coactivator of the mastermind-like proteins (MAML). The complex can then activate target gene transcription. Diallyl trisulfide (DATS) treatment increases expression of tumor suppressor microRNAs: miR-143 and miR-145. MicroRNAs bind to Notch1 mRNA and results in mRNA degradation with no translation of Notch1 protein. Curcumin downregulates transcription and translation Notch1 and downstream genes Hes-1, Hey-1, and Hey-2 of the nucleus