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Murrayanine Induces Cell Cycle Arrest, Oxidative Stress, and Inhibition of Phosphorylated p38 Expression in A549 Lung Adenocarcinoma Cells.
- Source :
-
Medical science monitor : international medical journal of experimental and clinical research [Med Sci Monit] 2019 Mar 17; Vol. 25, pp. 2002-2008. Date of Electronic Publication: 2019 Mar 17. - Publication Year :
- 2019
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Abstract
- BACKGROUND Murrayanine is a carbazole alkaloid derived from Murraya koenigii, which has been used in traditional Chinese medicine in the treatment of cancer. This study aimed to investigate the effects of murrayanine on human lung adenocarcinoma cells in vitro and to investigate the mechanisms of its action. MATERIAL AND METHODS A549 human lung adenocarcinoma cells and MRC-5 human lung fibroblasts were grown in culture, and an MTT assay determined cell viability. Cells were treated for 24 h with increasing doses of murrayanine (0, 9, 18, and 36 µM). Fluorescence, using 4', 6-diamidino-2-phenylindole (DAPI), acridine orange, ethidium bromide, and propidium iodide (PI), were used for the detection of apoptosis. The cell cycle was studied with fluorescence-activated cell sorting (FACS), and Western blot evaluated protein expression. RESULTS Murrayanine treatment resulted in significant dose-dependent inhibition of the growth of A549 cells (p<0.05), with an IC₅₀ of 9 µM, and arrested the cells at the G2/M phase of the cell cycle, reduced the expression of cyclin D and E, CDK2, 4, and 6, and increased the expression of p21 and p27. Murrayanine treatment increased apoptosis of the A549 cells and increased cleaved of caspase-3 and caspase-9, and the Bax/Bcl-2 ratio. Murrayanine treatment increased levels of reactive oxygen species (ROS), disrupted the mitochondrial membrane potential, inhibited invasion, and inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) of the A549 cells. CONCLUSIONS Murrayanine induced cell cycle arrest, oxidative stress, and inhibited the expression of phosphorylated p38 in A549 adenocarcinoma cells.
- Subjects :
- A549 Cells
Adenocarcinoma drug therapy
Apoptosis drug effects
Carbazoles metabolism
Caspase 3 drug effects
Caspase 9 drug effects
Cell Cycle drug effects
Cell Cycle Checkpoints drug effects
Cell Division drug effects
Cell Line, Tumor
Cell Proliferation drug effects
China
G2 Phase drug effects
Humans
Lung Neoplasms pathology
Oxidative Stress drug effects
Phosphorylation
Proto-Oncogene Proteins c-bcl-2 drug effects
Reactive Oxygen Species metabolism
Signal Transduction drug effects
p38 Mitogen-Activated Protein Kinases drug effects
Adenocarcinoma of Lung drug therapy
Carbazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1643-3750
- Volume :
- 25
- Database :
- MEDLINE
- Journal :
- Medical science monitor : international medical journal of experimental and clinical research
- Publication Type :
- Academic Journal
- Accession number :
- 30879017
- Full Text :
- https://doi.org/10.12659/MSM.913873