Moreover, nobiletin effectively suppressed SP-1 and CREB expressions, these findings are consistent with those in reports on leukemia cells [51], cholangiocarcinoma cells [52] and osteosarcoma cells [53], implicating the importance of NF-κB and CREB in the regulation of MMP-2 and MMP-9 in U2OS and HOS. This evidence concerns the gene MMP2 and osteosarcoma.