A novel all-trans retinoid acid derivative N-(3-trifluoromethyl- phenyl)- retinamide inhibits lung adenocarcinoma A549 cell migration through down-regulating expression of myosin light chain kinase.

Ting-Ting Fan,Qing Zhou,Yuan Wang,Yin-Feng Wang,Fei-Hu Chen,Shu-Yu Gui,Ying Cheng

doi:10.7314/apjcp.2014.15.18.7687

Abstract

To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)- retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down- regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.

Highlights

Malignant tumors are part and parcel of primary causes leading to death of human beings in nowadays
Aim: To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of al its drawbacks. N- (3-trifluoromethyl-phenyl)-retinamide (ATPR) inhibiting of A549 cell migration
Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA and PD98059 on the migration of A549 cells

Summary

Introduction

Malignant tumors are part and parcel of primary causes leading to death of human beings in nowadays. Due to the difficulty of early diagnosis and the poor effects of traditional therapy, including surgical operation and chemotherapy, cancer curing is still a worldwide challenge. Tracking back to twenty years ago, Chinese scientists were the pioneer to use ATRA to induce cell differentiation of acute promyelocytic leukemia (APL) (Huang et al, 1988) and acquired complete remission (Chen et al, 1992b; Wang et al, 1999e). A series of studies of ATRA on APL and solid tumors were developed at full blast. Vast researches indicated that ATRA could induce cell differentiation and inhibit invasion and migration of multiple solid tumor cells, including breast cancer, gastric carcinoma and colon cancer, and so on (Bengtsson et al, 2013; Hu et al, 2012a; 2014b Wang et al, 2013a; Zhang et al, 2013b; 2014a; Garattini et al, 2014; Tang et al, 2014). It is requisite to modify the structure and properties of ATRA to overcome

Objectives

Methods

Results

Conclusion