Abstract
BackgroundThis study aimed to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and its underlying mechanisms in human lung adenocarcinoma A549 cells in vitro.Methods5FEM was obtained by the chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle, mitochondrial membrane potential (ΔΨm), scratch test, colony formation, and the expression levels of the key survivin pathway-related genes in A549 were evaluated.Results5FEM could significantly inhibit A549 cell growth; induce cell apoptosis; increase G0/G1 population; reduce ΔΨm; inhibit cell migration and colony formation; upregulate caspase-9, P21, and Bax expression levels; and downregulate PARP, survivin, and Bcl-2 expression level.ConclusionThese results enhanced our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.
Highlights
This study aimed to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and its underlying mechanisms in human lung adenocarcinoma Human lung adenocarcinoma (A549) cells in vitro
Survivin expression level on A549 cells with LV5-homo Lentivirus human survivinoverexpression plasmid vector (BIRC5) transfection Human lung adenocarcinoma A549 cell line was transfected with LV5-Homo BIRC5
The results showed that the survivin expression level in A549 cells was increased significantly in LV5-Homo BIRC5 transfection group than control group, but the change between LV5NC-transfected and normal A549 cells was not significant (Fig. 2)
Summary
This study aimed to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and its underlying mechanisms in human lung adenocarcinoma A549 cells in vitro. Despite the availability of chemotherapy regimens, the Inhibitor of apoptosis protein (IAP) family regulates apoptosis. As a new member of the recently discovered IAP family, survivin plays an important role in cell apoptosis and cell cycle regulation [4]. In 1997, Ambrosini et al [5] firstly isolated survivin from the human genome library using effect cell protease receptor 1 cDNA and found that it is still the strongest apoptotic inhibitor protein. The gene is located on human chromosome 17q25, has a full length of ~ 14.5 kb, contains four exons and three introns, and encodes a survivin protein with a molecular weight of 16.3 kD and contains 142 amino acids [6].
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