In contrast, Lee et al. [26] showed in human hepatoma cells that p38, but not ERK, mediated the upregulation of Nrf2 and HO-1 by andrographolide, while in endothelial cells, although andrographolide activated ERK, the induction of HO-1 was dependent on phosphatidylinositol-3 kinase/protein kinase B, rather than on ERK [27]. This evidence concerns the gene MAPK1 and hepatocellular carcinoma.