After confirming SFE could upregulate MAP2K3 and GADD45B expression in vitro and in vivo (Fig. 5a–c), and considering GADD45B was the target gene of p5331–33, we guessed there was a specific cascade, MAP2K3/GADD45B-p38-p53-GADD45B, in SFE-treated esophageal cancer cells. Here, MAP2K3 is linked to esophageal cancer.