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Fig. 2 | Journal of Hematology & Oncology

Fig. 2

From: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy

Fig. 2

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

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