KDR and neoplasm: Moreover, natural compounds can target multiple key regulators, e.g., safranal, a metabolite of Crocus sativus, in the case where tumor angiogenesis significantly affects the strong interplay of hepatocellular carcinoma cells, endothelial cells, and multiple signaling molecules involved in tumor angiogenesis by downregulation of the in vitro expression of HIF-1α, VEGF, VEGFR2, p-AKT, p-ERK1/2, MMP9, p-FAK, and p-STAT3 [3].