1. Department of Optometry, Asia University, Taichung, Taiwan.
2. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
3. Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University, and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
4. Department of Nutrition, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan.
5. Chinese Medicine Department, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
6. Emergency department, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan.
7. Department of Occupational Safety and Health, Chung Shan Medical University, Taiwan; Department of Occupational Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
#These authors contributed equally to this work.
Fine particulate matter (PM2.5) is the critical cause of lung cancer and can further promote tumor cell migration and invasion. This study investigated the effects of luteolin, an antiangiogenic flavonoid agent, on blocking aqueous extract PM2.5-prompted cancer progression. We observed that luteolin reduced cell migration and the expression of pro-metastatic factors pro-matrix metalloproteinase (MMP)-2 and intercellular adhesion molecule (ICAM)-1 in PM2.5-exposed H460 lung cancer cells. Luteolin treatment also reduced the transduction of PM2.5-induced epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) cascade signaling. Furthermore, the reduction of MMP-2 expression and ICAM-1 production by luteolin in PM2.5-stimulated H460 cells is EGFR-PI3K-AKT pathway dependent. These results suggest that luteolin exhibits antitumor progression by inhibiting EGFR-PI3K-AKT pathway.
Keywords: luteolin, PM2.5, lung cancer, metastasis, EGFR-PI3K-AKT signalling