ผลของลูทีโอลินต่อการเคลื่อนที่และการลุกลามของเซลล์มะเร็งปอด

Abstract

Non-small cell lung cancer is the leading cause of cancer death. Chemotherapy is often considered to target cancer, but still experiencing recurrence and high mortality rate in the patients. Luteolin is a flavonoid which has been investigated for the anticancer properties; however, its anticancer mechanisms remain unclear. The objective of this study is to examine the effect and the molecular mechanism of luteolin on the inhibition of cell migration progression in non-small cell lung cancer. Cytotoxicity of luteolin (5 , 10, 20, 40, 50 and 80 μM) on lung cancer A549 cells and normal lung fibroblast MRC-5 cells was assessed by MTT assay. The apoptosis cell death was also observed. In addition, the anti-migratory and anti-invasive potential of luteolin on lung cancer cell lines was determined by scratch wound healing and invasion assays. The protein expression was also examined by western blotting. The result showed that luteolin at the concentration of 5-20 μM was not toxic to the lung cancer cells A549 and its IC50 at 24 h was 78.86 μM. Exposure of A549 cells to luteolin at the concentration of 40-80 μM resulted in apoptotic cell death. Besides, the treatment of MRC-5 cells with luteolin at all concentrations showed no toxicity. Luteolin 20-40 μM was found to inhibit migration and invasion as well as the formation of filopodia and lamellipodia in A549 cells. The protein expression of the signaling molecules including Rac1, Cdc42, RhoA, FAK and Src was determined by using western blotting and found that luteolin (20-40 μM) significantly decreased the phosphorylation of FAK and its downstream targets, Src and decreased protein expression of cell motility-related Rac1, Cdc42 and RhoA when compared to the control. The findings from this study indicate that luteolin suppresses migration and invasion of lung cancer cells by altered cell motility-related protein expression, suggesting the potential role of luteolin for the development of cancer therapy.