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KMID : 1123920180320030157
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Korean Journal of Oriental Physiology and Pathology
2018 Volume.32 No. 3 p.157 ~ p.164
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Reactive Oxygen Species (ROS) Generation Contributes to the Synergistic Anticancer Effect of Astragalus Membranaceus and Adenophora Triphylla Var. Japonica in H1299 Human Lung Carcinoma Cells
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Min Tae-Rin
Park Hyun-Ji
Park Shin-Hyung
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Abstract
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This study was designed to investigate the mechanism of the synergistic anticancer effect of Astragalus membranaceus (AM) and Adenophora triphylla var. japonica (AT) in H1299 human lung carcinoma cells. A combined treatment of ethanol extract of AM (EAM) and AT (EAT) explosively increased the reactive oxygen species (ROS) generation in H1299 cells compared to the single treatment of each of them. Co-treatment of N-acetyl-L-cysteine (NAC) with EAM and EAT markedly enhanced the cell viability and suppressed apoptosis in H1299 cells, suggesting that ROS generation contributed to the anticancer effect of EAM and EAT. Interestingly, the combined treatment of EAM and EAT down-regulated p-AKT in H1299 cells, which was abrogated by NAC treatment. These results clearly indicated that ROS generation mediated the inactivation of AKT. Co-treatment of LY294002 with EAM and EAT significantly reduced the cell viability at a concentration which EAM and EAT didn’t show any cytotoxicity. In addition, the recovery of cell viability by co-treatment of NAC with EAM and EAT was quite reversed by LY294002 treatment, which confirmed that the inactivation of AKT played a pivotal role in ROS-mediated apoptosis. Taken together, our results demonstrated that the synergistic anticancer effect of EAM and EAT was mediated by ROS generation and inactivation of AKT. We provide a valuable preclinical data for the development of more effective combination of AM and AT to treat lung cancer.
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KEYWORD
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Astragalus membranaceus, Adenophora triphylla var. japonica, Combination therapy, Lung cancer, ROS generation
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