Inotilone from Inonotus linteus suppresses lung cancer metastasis in vitro and in vivo through ROS-mediated PI3K/AKT/MAPK signaling pathways

Metastasis is one of the main causes of mortality in cancer patients. Inotilone, a major component of Inonotus linteus, is a traditional Chinese medical herb. In this study, MTT results showed that inotilone had no obvious cytotoxicity. Animal model results revealed that inotilone suppressed cancer metastatic efficacy. Serum results showed that inotilone reduced the activity of matrix metalloproteinase (MMP)-2 and -9 and tumor necrosis factor alpha (TNF-α) activity as well as NO content. Additionally, inotilone affected MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-2 protein expression and improved the activity of the antioxidant enzymes in the lung tissues of LLC-bearing mice. In addition, cell experimental results showed that inotilone reduced the activity of MMP-2/-9 and inhibited the ability for cellular migration and invasion. Inotilone decreased interleukin (IL)-8 expression in A549 cells. Western blot results revealed that inotilone affected the protein expression of MMPs, nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, anti-oxidant enzymes, mitogen activated protein kinase (MAPK), focal adhesion kinase (FAK), phosphoinositide-3 kinase (PI3K)-AKT, and nuclear factor (NF)κB. Therefore, we propose that inotilone is a potential therapeutic candidate against metastatic lung cancer cells.