Fucosterol exerts antiproliferative effects on human lung cancer cells by inducing apoptosis, cell cycle arrest and targeting of Raf/MEK/ERK signalling pathway

Abstract

Background: Phytochemicals have attained tremendous attention as the chemo-preventive and chemotheruptic agents. Fucosterol is a phytosterol that in prevalently found in marine algae and many other plant species. Previous studies have indicated the potential of fucosterol as an anticancer agent. However, the information on the anticancer activity of fucosterol against lung cancer as well as several other types of cancers is scantly.

Purpose: The present study was designed to investigate the anticancer activity of fucosterol against a panel of lung cancer cell lines.

Methods: MTT and colony formation assays were used to determine the cell viability. DAPI and annexin V/PI staining assays were used for the detection of apoptosis. Cell cycle analysis was performed by flow cytometery. Boyden chamber assay was used to monitor cell migration and western blot analysis was used to determine the protein expression. In vivo evaluation was carried out in xenografted mice models.

Results: The results indicated that fucosterol inhibits the growth of the lung cancer cell lines. However, the anticancer effects were more profound against the A549 and SK-LU-1 cancer cells (IC_50, 15 µM). In contrast, the anticancer effects of fucosterol on the non-cancerous lung cell lines were minimal. Further investigation revealed that the anticancer effects of fucosterol on the A549 and SK-LU-1 cells are due to the induction of apoptosis. Fucosterol significantly enhanced the expression of Bax and cleaved caspase-3 which was concomitant with decline in the expression of Bcl-2. Fucosterol also triggered G₂/M cell cycle arrest of the A549 and SK-LU-1 cells which was associated with decrease in the expression of Cdc2, Cyclin A, Cyclin B1 and upregulation of the negative regulators of cell cycle progression (p21^Cip1, and p27^Kip1). Moreover, fucosterol could also inhibit the invasion of A549 and SK-LU-1 cells. Finally fucosterol could also inhibit the growth of xenografted tumours in mice.

Conclusion: Taken together, fucosterol inhibits the growth of lung cancer cells and may prove to be a lead molecule for the treatment of lung cancer.

Keywords: Apoptosis; Cell cycle; Fucosterol; Invasion; Lung cancer.