Jeong Hyungmin, Phan Ai N H, Choi Jong-Whan
Wonju High School, Yonsei University, Wonju, Gangwon-Do, Republic of Korea.
Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-Do, Republic of Korea.
Pharmacogn Mag. 2017 Oct-Dec;13(52):595-599. doi: 10.4103/pm.pm_535_16. Epub 2017 Nov 13.
Polyphenolic phytochemicals are natural compounds, easily found in fruits and vegetables. Importantly, polyphenols have been intensively studied as excellent antioxidant activity which contributes to anticancer function of the natural compounds. Lung cancer has been reported to mainly account for cancer-related deaths in the world. Moreover, epidermal growth factor receptor tyrosine kinase inhibitor (TKI) resistance is one of the biggest issues in cancer treatment, especially in nonsmall cell lung cancer (NSCLC). Even though several studies both in preclinical and clinical trials have showed promising therapeutic effects of polyphenolic compounds in anticancer therapy, the function of the natural compounds in TKI-resistant (TKIR) lung cancer remains poorly studied.
The aim of this study is to screen polyphenolic compounds as potential anticancer adjuvants which suppress TKIR lung cancer.
Colony formation and thiazolyl blue tetrazolium blue assay were performed in the pair-matched TKI-sensitive (TKIS) versus TKIR tumor cell lines to investigate the therapeutic effect of polyphenolic compounds in TKIR NSCLC.
Our data show that equol, kaempferol, resveratrol, and ellagic acid exhibit strong anticancer effect in HCC827 panel. Moreover, the inhibitory effect of most of tested polyphenolic compounds was highly selective for TKIR lung cancer cell line H1993 while sparing the TKIS one H2073.
This study provides an important screening of potential polyphenolic compounds for drug development to overcome TKI resistance in advanced lung cancer.
The study provides an important screening of potential polyphenolic compounds for drug development to overcome tyrosine kinase inhibitor (TKI) resistance in advance lung cancerEquol, kaempferol, resveratrol, and ellagic acid show strong anticancer effect in HCC827 panel, including TKI-sensitive (TKIS) and TKI-resistant clonesThe inhibitory effect of polyphenolic compounds such as equol, kaempferol, resveratrol, ellagic acid, gallic acid, p-Coumaric, and hesperidin is highly selective for TKI-resistant lung cancer cell line H1993 while sparing the TKIS one H2073. EGFR: Epidermal growth factor receptor, EMT: Epithelial-to-mesenchymal transition, GTP: Green tea polyphenols, IGF1R: Insulin-like growth factor 1 receptor, MET: Met proto-oncogene, MTT: Thiazolyl blue tetrazolium blue, NSCLC: Non-small cell lung cancer, ROS: Reactive oxygen species, RTK: Receptor tyrosine kinase, STAT3: Signal transducer and activator of transcription 3, TKIR: TKI-resistant, TKIs: Tyrosine kinase inhibitors, TKIS: TKI-sensitive.
多酚类植物化学物质是天然化合物，在水果和蔬菜中很容易找到。重要的是，多酚类物质因其出色的抗氧化活性而受到深入研究，这种活性有助于这些天然化合物发挥抗癌作用。据报道，肺癌是全球癌症相关死亡的主要原因。此外，表皮生长因子受体酪氨酸激酶抑制剂（TKI）耐药性是癌症治疗中的最大问题之一，尤其是在非小细胞肺癌（NSCLC）中。尽管临床前和临床试验的多项研究均显示多酚类化合物在抗癌治疗中具有有前景的治疗效果，但这些天然化合物在TKI耐药（TKIR）肺癌中的作用仍研究不足。
本研究旨在筛选可作为潜在抗癌佐剂、抑制TKIR肺癌的多酚类化合物。
在配对的TKI敏感（TKIS）与TKIR肿瘤细胞系中进行集落形成实验和噻唑蓝比色法，以研究多酚类化合物对TKIR NSCLC的治疗效果。
我们的数据表明，雌马酚、山奈酚、白藜芦醇和鞣花酸在HCC827细胞组中表现出强大的抗癌作用。此外，大多数测试的多酚类化合物对TKIR肺癌细胞系H1993具有高度选择性抑制作用，而对TKIS细胞系H2073则无影响。
本研究为药物研发提供了重要的潜在多酚类化合物筛选，以克服晚期肺癌中的TKI耐药性。
该研究为药物研发提供了重要的潜在多酚类化合物筛选，以克服晚期肺癌中的酪氨酸激酶抑制剂（TKI）耐药性。雌马酚、山奈酚、白藜芦醇和鞣花酸在HCC827细胞组中表现出强大的抗癌作用，包括TKI敏感（TKIS）和TKI耐药克隆。多酚类化合物如雌马酚、山奈酚、白藜芦醇、鞣花酸、没食子酸、对香豆酸和橙皮苷对TKI耐药肺癌细胞系H1993具有高度选择性抑制作用，而对TKIS细胞系H2073则无影响。EGFR：表皮生长因子受体，EMT：上皮-间质转化，GTP：绿茶多酚，IGF1R：胰岛素样生长因子1受体，MET：原癌基因Met，MTT：噻唑蓝比色法，NSCLC：非小细胞肺癌，ROS：活性氧，RTK：受体酪氨酸激酶，STAT3：信号转导和转录激活因子3，TKIR：TKI耐药，TKIs：酪氨酸激酶抑制剂，TKIS：TKI敏感
