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.

Abstract

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 ATPR inhibiting of A549 cell migration.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Ting-Ting Fan, Ying Cheng, Yin-Feng Wang, Shu-Yu Gui, Fei-Hu Chen, Qing Zhou, Yuan Wang
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 18 Pg. 7687-92 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 25292047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Tretinoin
• retinamide
• Myosin-Light-Chain Kinase

Topics

• Adenocarcinoma (drug therapy, enzymology, pathology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Cycle
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Lung Neoplasms (drug therapy, enzymology, pathology)
• Myosin-Light-Chain Kinase (antagonists & inhibitors, metabolism)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)
• Tretinoin (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured