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

Life Sciences
Enxia WangLidan Sun

Abstract

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. 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. 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 w...Continue Reading

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Citations

Jul 22, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nicola SassiLucia Biasutto
Dec 1, 2018·Journal of Cellular Physiology·Raedeh SaraeiAli Hassanzadeh
May 18, 2019·Journal of Cellular Biochemistry·Yangyang FanLiming Tao
Sep 16, 2020·International Journal of Molecular Sciences·Monica BenvenutoRoberto Bei
Aug 3, 2019·European Journal of Medicinal Chemistry·Lucia BiasuttoMario Zoratti
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zile HuangJiangang Wang

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