Neuroprotective and anticancer effects of 7-Methoxyheptaphylline via the TAK1 pathway

7-Methoxyheptaphylline (7-MH) is a carbazole extracted from Clausena harmandiana, a medicinal plant that is used to treat headaches and stomachaches. The aim of the present study was to examine the neuroprotective effects and anticancer activity of 7-MH. Cell death was assessed using an MTT assay and flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis. An animal model was used to test anti-metastasis. The interactions between 7-MH and the molecular target were observed using molecular docking. The results revealed that 7-MH provided protection against hydrogen peroxide (H(2)O(2))-induced neuronal cell death. In cancer cells, 7-MH induced SH-SY5Y, 4T1, HT29, HepG2, and LNCaP cell death. 7-MH inhibited metastasis of HT29 cells in vitro and 4T1-Luc cells in vitro and in vivo. 7-MH inhibited proteins, including P-glycogen synthase kinase (GSK)-3, and cleaved caspase-3, but it activated anti-apoptotic proteins in H(2)O(2)-induced SH-SY5Y cell death. By contrast, 7-MH activated the cleaving of caspase-3 and GSK-3, but it suppressed anti-apoptotic proteins in SH-SY5Y cells. 7-MH reduced the levels of NF-κB and STAT3 in 4T1 cells; phospho-p65, Erk, and MAPK13 in LNCaP cells; and phospho-Erk and matrix metalloproteinase-9 in HT29 cells. Molecular docking analysis showed that 7-MH targets TAK1 kinase. The present study indicated that 7-MH induced apoptosis of cancer cells and provided protection against H(2)O(2)-induced neuron cell death via TAK1 kinase.