Genistein inhibits the proliferation, migration and invasion of the squamous cell carcinoma cells via inhibition of MEK/ERK and JNK signalling pathways

Purpose: The main purpose of the current research work was to investigate the anticancer activity of Genistein - a plant derived isoflavone - in squamous cell carcinoma SK-MEL-28 (SCC) cells along with studying its effects on cellular apoptosis, DNA damage, cell migration and invasion and MEK/ERK/JNK signalling pathway. Methods: Cell proliferation was examined by CCK-8 (Cell Counting Kit-8) assay while the effects on apoptosis were evaluated by DAPI staining and Comet assay using fluorescence microscopy. Transwell assay was used for checking the effects on cell migration and invasion while western blot method was used to evaluate the effects on the expression of MEK/ERK/JNK proteins. Results: The results showed that Genistein led to dose-dependent cytotoxic effects in these cells showing an IC50 value of 14.5 mu M. It also led to dose-dependent apoptosis and induced DNA damage as shown by fluorescence microscopy. Genistein also inhibited cell migration and invasion dose-dependently, along with inhibiting matrix metalloproteinase (MMP)-9 expression. Genistein also led to inhibition of the expression of p-JNK with no apparent effects on the total JNK expression. It also showed significant and dose-dependent inhibition of the expression of p-MEK and p-ERK proteins. Conclusions: Genistein has a significant anticancer activity in SK-MEL-28 human SCC cells, inducing apoptosis, DNA damage, cell migration and invasion and inhibiting MEK/ERK and JNK signalling pathway.