7,8-Dihydroxycoumarin inhibits A549 human lung adenocarcinoma cell proliferation by inducing apoptosis via suppression of Akt/NF-κB signaling

作者：Yue Wang, Changfeng Li, Liming Pan, Zhongli Gao · 发表于：Experimental and Therapeutic Medicine · 年份：2013 · DOI：10.3892/etm.2013.1054 · 被引用次数：27 · 研究领域：Synthesis and biological activity、Synthesis of Organic Compounds、Bioactive natural compounds

The Akt/NF-κB pathways are involved in numerous anti-apoptotic and drug-resistance events that occur in non‑small cell lung cancer (NSCLC). In the present study, the role of 7,8-dihydroxycoumarin in the regulation of the anti‑apoptotic Akt and NF-κBp65 signaling pathways was explored. A549 human lung adenocarcinoma cells were exposed to 7,8-dihydroxycoumarin with a final concentration of 25, 50 and 100 µmol/l for 48 h. Quantitative polymerase chain reaction (PCR) and western blotting were performed to detect mRNA and protein expression, respectively. The MTT assay was performed to detect cell proliferation. The results demonstrated that anti‑apoptotic phospho-Akt1 (pAkt1), phospho-IκBα (pIκBα), NF-κBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a concentration-dependent manner. At a concentration of 100 µmol/l, the anti-apoptotic NF-κBp65 and Bcl-2 mRNA expression levels decreased 0.12 (5.82/48.5, treated/control)-fold and 0.17 (6.7/39.4, treated/control)-fold, respectively. The pro-apoptotic caspase-3 mRNA was upregulated 4.43 (39.4/8.9, treated/control)‑fold. The anti‑apoptotic pAkt1, pIκBα, NF-κBp65 and Bcl-2 proteins were downregulated, with blot grayscale values of 7.3 (vs. 52.4 control), 4.3 (vs. 42.2 control), 5.08 (vs. 44.5 control) and 5.92 (vs. 38.5 control), respectively. The pro-apoptotic caspase-3 was upregulated to a blot grayscale value of 27.8 (vs. 5.8 control). The proliferative activity of A549 cells was reduced significantly co...