Anti-cancer Effects of Polyphenolic Compounds in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer.

ABSTRACT

BACKGROUND: 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. OBJECTIVE: The aim of this study is to screen polyphenolic compounds as potential anticancer adjuvants which suppress TKIR lung cancer. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: This study provides an important screening of potential polyphenolic compounds for drug development to overcome TKI resistance in advanced lung cancer. SUMMARY: 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. Abbreviations used 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.