Through the downregulation of the expressions of cyclin D1 and CDK4 (related to G1 phase), as well as cyclin B1 and CDK1 (related to G2/M phase), melatonin inhibits the proliferation of human osteosarcoma MG-63 cells [65]; meanwhile, the inhibition of the ERK1/2 signaling pathway is involved in the melatonin’s anti-proliferative effect, induction of G1 and G2/M phase cell arrest, and downregulation of expressions of cyclin D1, CDK4, cyclin B1, and CDK1 in MG-63 cells [66]. Here, CDK4 is linked to osteosarcoma.