Elevated expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the development of the multidrug resistance phenotype in patients with advanced non-small-cell lung cancer (NSCLC). Due to the lack of U.S. Food and Drug Administration (FDA)-approved synthetic inhibitors of ABCG2, significant efforts have been invested in discovering bioactive compounds of plant origin that are capable of reversing ABCG2-mediated multidrug resistance in cancer cells. Sophoraflavanone G (SFG), a phytoncide isolated from the plant species Sophora flavescens, is known to possess a wide spectrum of pharmacological activities, including antibacterial, anti-inflammatory, antimalarial, and antiproliferative effects. In the present study, the chemosensitizing effect of SFG in ABCG2-overexpressing NSCLC cells was investigated. Experimental results demonstrate that at subtoxic concentrations SFG significantly reversed ABCG2-mediated multidrug resistance in a concentration-dependent manner. Additional biochemical data and in silico docking analysis of SFG to the inward-open conformation of human ABCG2 indicate that SFG inhibited the drug transport function of ABCG2 by interacting with residues within the transmembrane substrate-binding pocket of ABCG2. Collectively, these findings provide evidence that SFG has the potential to be further tested as an effective inhibitor of ABCG2 to improve the efficacy of therapeutic drugs in patients with advanced NSCLC.

中文翻译：

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Sophoraflavanone G 使 ABCG2 过表达的多药耐药性非小细胞肺癌细胞对化疗药物重新敏感

癌细胞中 ATP 结合盒 (ABC) 药物转运蛋白 ABCG2 的表达升高有助于晚期非小细胞肺癌 (NSCLC) 患者多药耐药表型的发展。由于缺乏美国食品和药物管理局 (FDA) 批准的 ABCG2 合成抑制剂，在发现能够逆转 ABCG2 介导的癌细胞多药耐药性的植物来源生物活性化合物方面投入了大量精力。Sophoraflavanone G (SFG)，一种从植物Sophora flavescens 中分离的植物杀菌素已知具有广泛的药理活性，包括抗菌、抗炎、抗疟和抗增殖作用。在本研究中，研究了 SFG 在 ABCG2 过表达 NSCLC 细胞中的化学增敏作用。实验结果表明，在亚毒性浓度下，SFG 以浓度依赖性方式显着逆转 ABCG2 介导的多药耐药性。额外的生化数据和 SFG 与人 ABCG2 的向内开放构象的计算机对接分析表明，SFG 通过与 ABCG2 跨膜底物结合口袋内的残基相互作用来抑制 ABCG2 的药物转运功能。总的来说，