METHODS: Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT. The effects of berberine and lapatinib on MAPK and PI3K pathways in MDA-MB231 and MCF-7 cells were evaluated using immunoflorescence assays, and the amounts of phosphorylated kinases were compared to total kinases after treating with different concentrations of berberine.
RESULTS: Simulations showed berberine accurately interacted with EGFR, AKT, P38, and ERK1/2 active sites in silico (scores = -7.57 to -7.92 Kcal/mol) and decreased the levels of active forms of corresponding enzymes in both cell lines; however, berberine binding to p38 showed less stability. Cytotoxicity analysis indicated that MDA-MB231 cells were resistant to berberine compared to MCF-7 cells [72 h IC50 = 50 versus 15 μM, respectively). Also, lapatinib strongly activated AKT but suppressed EGFR in MDA-MB231 cells. The activity of EGFR, AKT, P38, and ERK1/2 were affected by berberine; however, berberine dramatically reduced EGFR and AKT phosphorylation.
CONCLUSION: By way of its multikinase inhibitory effects, berberine might be a useful replacement for lapatinib, an EGFR inhibitor which can cause acquired drug resistance in patients.
METHODS: Among several species, Typhonium blumei, T. flagelliforme, T. divaricatum and T. giganteum were extensively studied due to the presence of a class of secondary metabolites. All the available reports on Typhonium were included and discussed in this article.
RESULTS: Until now several groups of compounds, namely amino acids (1, 2), cinnamic acid (3), fatty acids (4-14), glycerol derivatives (15-18) and cerebrosides (19-34), flavonoids (35), hydantoins (36-38), lignin monomers (39-44), nucleobases (45-48), pheophorbides (49-52), phthalate (53), terpene and steroids (54-59) and vitamins (60, 61) were isolated and characterized from Typhonium. These phytochemicals were investigated for their anticancer properties, and results confirmed the promising growth inhibitory effect and anticancer activities against human lung, breast, prostate and colon cancer cells. The anticancer activity of these compounds appears to be mediated through the induction of apoptotic cell death. These phytochemicals further reported to exhibit other pharmacological efficacies, including anti-inflammatory, antioxidant, antiviral, anti-allergic, neuroprotective and hepato-protective properties.
CONCLUSION: This is the first review to summarize the anticancer properties of all isolated compounds of Typhonium genus with confirmed chemical structures. Further advanced studies are necessary to establish the detailed signaling pathways that are involved in the anticancer property of the compounds.