EGFR and ERK activation resists flavonoid quercetin-induced anticancer activities in human cervical cancer cells in vitro

Xin Chen, Pengli Xu, Huijun Zhang, Xiaosan Su, Lihua Guo, Xuhong Zhou, Junliang Wang, Peng Huang, Qingzhi Zhang, Ruifen Sun

Research output: Contribution to journalArticlepeer-review

Abstract

In the present study, due to the complex and numerous targets of Sarcandrae Herb (also known as Zhong Jie Feng), network pharmacology was performed to analyze its therapeutic effect on 2 cervical cancer cell lines, which could assist with the development of novel therapies. The results suggested that the natural flavonoid quercetin (Que), the effective antitumor ingre- dient in SH, which is widely present in a variety of plants, may depend on the target, EGFR. Previous studies have shown that EGFR serves a crucial role in the occurrence and development of cervical cancer, but its downstream molecules and regula- tory mechanisms remain unknown. The anti-cervical cancer cell properties of Que, which are present in ubiquitous plants, were examined in vitro to identify the association between Que and its underlying pathway using MTT assays, flow cytometry, western blot analysis and Transwell assays. It was found that Que reduced cervical cancer cell viability, promoted G2/M phase cell cycle arrest and cell apoptosis, as well as inhibited cell migration and invasion. The Tyr1068 phosphorylation site of EGFR and the corresponding ERK target were also examined and the 2 kinases were markedly activated by Que. Furthermore, the EGFR inhibitor, afatinib and the ERK inhibitor, U0126 blocked the increase of EGFR and ERK phos- phorylation, and resulted in a notable enhancement of apoptosis and cell cycle arrest. Therefore, to the best of our knowledge, the current results provided the first evidence that EGFR and ERK activation induced by Que could resist Que-induced anticancer activities. On this basis, the present study determined the role of EGFR and the underlying signaling pathways involved in the anti-cervical cancer malignant behavior induced by Que and identified the negative regulatory association.

Original languageEnglish
Article number754
JournalOncology Letters
Volume22
Issue number5
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Cervical cancer
  • EGFR
  • ERK
  • Negative regulatory association
  • Quercetin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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