Dipotassium Glycyrrhizinate Inhibits Histamine-Induced Proliferation by Suppressing Cell Cycle and P38/FAK Pathway of Lung Cancer Cells In-Vitro

Abstract

Histamine is released from activated mast cells which have been found around tumor tissue area. The aim of this study was to examine the function of histamine on human lung cancer cell line A549 cell; to investigate the anti-histamine effects of dipotassium glycyrrhizinate (DG) on histamine mediated proliferation and migration of A549 cells and to explore the potential inhibitory mechanism of DG on lung cancer cell metastasis. The in-vitro histamine/A549 cells model was established, the cell proliferation, migration and cell cycle were examined, and the intracellular glutathione (GSH) level and signal proteins were detected. Data showed that histamine promote cell viability, proliferation and migration, while DG inhibited the histamine-induced cell proliferation and migration. DG decreased histamine-induced expressions of FAK, matrix metalloproteinases-2/9 (MMP-2/9), P38, PCNA, and Bcl-2, and DG up-regulated Bax, P53 and Becline-1 expressions against histamine’s effects. DG altered the histamine-driven M-phase in cell cycle and decreased the histamine-elevated GSH content in A549 cells, leading to cell apoptosis. This study revealed that DG inhibited the histamine-induced cell proliferation and promoted cell apoptosis of A549 cells, implicating its potential therapeutic mechanisms on lung cancer cell proliferation, metastasis and development.