Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Molecules

Yi-Chiung Hsu¹  Chih-Ching Wu²  Tong-Hong Wang³  Yu-Wen Jiang³  Chi-Yuan Chen³  Yann-Lii Leu⁴  Kuo-Yen Huang⁵ 

[1] Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320, Taiwan;Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;Graduate Institute of Health Industry Technology and Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan;Graduate Institute of Natural Products, Chang Gung University, Taoyuan 333, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan;

关键词: daphne genkwa;    hydroxygenkwanin;    nsclc;    egfr;    apoptosis;   

DOI  :  10.3390/molecules25040941

来源: DOAJ

【 摘 要 】

Epidermal growth factor receptor (EGFR) is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC), which is the major type of lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) are the approved treatment for patients harboring activating mutations in the EGFR kinase. However, most of the patients treated with EGFR-TKIs developed resistance. Therefore, the development of compounds exhibiting unique antitumor activities might help to improve the management of NSCLC patients. The total flavonoids from Daphne genkwa Sieb. et Zucc. have been shown to contain antitumor activity. Here, we have isolated a novel flavonoid hydroxygenkwanin (HGK) that displays selective cytotoxic effects on all of the NSCLC cells tested. In this study, we employed NSCLC cells harboring EGFR mutations and xenograft mouse model to examine the antitumor activity of HGK on TKI-resistant NSCLC cells. The results showed that HGK suppressed cancer cell viability both in vitro and in vivo. Whole-transcriptome analysis suggests that EGFR is a potential upstream regulator that is involved in the gene expression changes affected by HGK. In support of this analysis, we presented evidence that HGK reduced the level of EGFR and inhibited several EGFR-downstream signalings. These results suggest that the antitumor activity of HGK against TKI-resistant NSCLC cells acts by enhancing the degradation of EGFR.

【 授权许可】

Unknown