Abstract

 
 
 
 Purpose: To determine the antitumor effect of demethoxycurcumin on lung cancer cells, as well as its effect on PI3K/AKT/m-TOR signalling, cellular apoptosis, cell migration and cell invasion.
 Methods: Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while AO/EB and annexin V/PI staining assays were used for apoptosis analysis in demethoxycurcumin-treated A-549 lung cancer cells. Transwell chamber assay was used to determine the effect of demethoxycurcumin on migration and invasion of A-549 cells. The expression levels of PI3K/AKT/m-TOR signalling and apoptosis-associated proteins in A-549 cells post- demethoxycurcumin treatment were determined by Western blotting assay.
 Results: Demethoxycurcumin markedly inhibited the proliferation of A-549 cells in a dose- and time- reliant fashion. The antiproliferative effect of demethoxycurcumin occurred via stimulation of apoptosis. The expression levels of Bax, Caspase-3 and Caspase-9 increased significantly, while Bcl-2 was significantly decreased in A-549 cells post-demethoxycurcumin treatment. Demethoxycurcumin substantially inhibited migration and invasion of A-549 cells, and blocked PI3K/AKT/m-TOR signalling pathway in these cells.
 Conclusion: Demethoxycurcumin induces anticancer effects on A-549 cells via targeting PI3K/AKT/mTOR signalling pathway. It induces cellular apoptosis and inhibits migration and invasion of A-549 cells. Thus, it is a promising anti-lung cancer agent.
 
 
 
Highlights
Cancer is a serious health problem that affects a significant percentage of the human population globally
The effect of demethoxycurcumin on the proliferation of A-549 Lung cancer (LC) cells was determined with MTT assay
It was observed that the percentage viability values at 0, 10, 20, 40 and 80 μM were 100, 90, 70, 42 and 17, after 48 h of demethoxycurcumin exposure
Summary
Cancer is a serious health problem that affects a significant percentage of the human population globally. Demethoxycurcumin has been shown to produce pro-apoptotic and proautophagic effects against several human cancer cell lines. The present study was undertaken to investigate the anticancer potential of demethoxycurcumin on LC cell line, as well as its effect on cellular apoptosis, PI3K/AKT/m-TOR signalling, cell migration and cell invasion. The effect of demethoxycurcumin on the proliferation of A-549 LC cells was determined with MTT assay. Determination of apoptosis using AO/EB dual fluorescent dye Apoptotic cell death in A-549 LC cells was investigated using AO/EB dual staining and annexin V/PI staining assays. The cells were seeded in 96-well plates and treated with demethoxycurcumin at different concentrations viz 20, 40 and 80 μM. The transwell chambers were incubated for 12 h, followed by fixation of the cells with alcohol for 10 min at 4 oC. Values of p < 0.05 were considered as indicative of statistically significant differences
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