Fig. 5
From: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy
PI3K-AKT-mTOR and RAS-RAF-MEK-ERK pathways. Growth factor binds to epidermal growth factor receptor and can proceed by two different pathways. For the PI3 pathway, the ligand activates tyrosine kinase receptor activity resulting in phosphorylation of receptor. PI3K binds to phosphorylated receptor and becomes activated. PI3K then binds to PIP2 on inner membrane and phosphorylates PIP2 to PIP3. PIP3 activates AKT via PDK1. AKT can then phosphorylate and activate protein mTOR which results in cell growth, cell proliferation, and cell survival. For the RAS-RAF pathway, growth factor binding to tyrosine kinase receptor activates RAS which in turn activates RAF. RAF activates MEK which phosphorylates ERK to decrease apoptosis and increase cell proliferation and growth. The compound sulforaphane suppresses the phosphorylation of AKT and ERK