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Article Publish Status: FREE
Abstract Title:

Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET.

Abstract Source:

Biomolecules. 2020 Feb 13 ;10(2). Epub 2020 Feb 13. PMID: 32070026

Abstract Author(s):

Ha-Na Oh, Mee-Hyun Lee, Eunae Kim, Ah-Won Kwak, Goo Yoon, Seung-Sik Cho, Kangdong Liu, Jung-Il Chae, Jung-Hyun Shim

Article Affiliation:

Ha-Na Oh

Abstract:

Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of(hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer.

Study Type : In Vitro Study

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