Advertisement

 

 

7-O-geranylquercetin-induced autophagy contributes to apoptosis via ROS generation in human non-small cell lung cancer cells.

7-O-geranylquercetin-induced autophagy contributes to apoptosis via ROS generation in human non-small cell lung cancer cells.
Author Information (click to view)

Wang EX, Zou BY, Shi L, Du LY, Zhu YY, Jiang YM, Ma XD, Kang XH, Wang CY, Zhen YH, Sun LD,


Wang EX, Zou BY, Shi L, Du LY, Zhu YY, Jiang YM, Ma XD, Kang XH, Wang CY, Zhen YH, Sun LD, (click to view)

Wang EX, Zou BY, Shi L, Du LY, Zhu YY, Jiang YM, Ma XD, Kang XH, Wang CY, Zhen YH, Sun LD,

Advertisement

Life sciences 2017 05 08180() 102-113 pii S0024-3205(17)30228-X
Abstract
AIMS
To investigate the antitumor effects of 7-O-geranylquercetin (GQ), a novel O-alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms.

MAIN METHODS
Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry.

KEY FINDINGS
GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N-acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis.

SIGNIFICANCE
Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer.

Submit a Comment

Your email address will not be published. Required fields are marked *

4 × one =

[ HIDE/SHOW ]