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Open AccessArticle

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

1
Department of Pharmacy, Mokpo National University, Jeonnam 58554, Korea
2
The China-US (Henan) Hormel Cancer Institute, Zhengzhou 450008, Henan, China
3
Basic Medical College, Zhengzhou University, Zhengzhou 450001, Henan, China
4
College of Pharmacy, Chosun University, Gwangju 61452, Korea
5
Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Jeonbuk National University, Jeonju 54896, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(2), 297; https://doi.org/10.3390/biom10020297
Received: 3 January 2020 / Revised: 10 February 2020 / Accepted: 10 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant Glycyrrhiza inflata, 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 MET (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.
Keywords: licochalcone D; non-small cell lung cancer; reactive oxygen species; apoptosis licochalcone D; non-small cell lung cancer; reactive oxygen species; apoptosis
MDPI and ACS Style

Oh, H.-N.; Lee, M.-H.; Kim, E.; Kwak, A.-W.; Yoon, G.; Cho, S.-S.; Liu, K.; Chae, J.-I.; Shim, J.-H. Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET. Biomolecules 2020, 10, 297.

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