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

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 ingredient 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 regulatory 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 G 2 /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 phosphorylation, 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.

RACK1 promotes the occurrence and progression of cervical carcinoma

“… 21 Previous studies have established that p21 can arrest the cell cycle in the G1 phase by interacting with cyclin D/CDK. 22 , 23 In our study, over‐expressed RACK1 led to p21 expression down‐regulation without affecting the expression of p53, indicating that p21 functions in an independent way on p53 in the development of CC with RACK1 dysregulation. However, considering the versatility of RACK1 in different types of human tumors, further research studies to clarify its function are still needed.…”

“…p21 was first identified as a downstream gene of p53, subsequent research showed that p21 functions as an important cell cycle regulator, involved in the process of cell growth, differentiation, aging and death 21 . Previous studies have established that p21 can arrest the cell cycle in the G1 phase by interacting with cyclin D/CDK 22,23 . In our study, over‐expressed RACK1 led to p21 expression down‐regulation without affecting the expression of p53, indicating that p21 functions in an independent way on p53 in the development of CC with RACK1 dysregulation.…”

comparative study of the effect of Cinnamomum zeylanicum extract and nanocomplex on some immunological and physiological parameters before and after MTX treatment loading

“…A natural flavonoid, widely present in many plants (X. Chen et al 2021) possessing strong antioxidant activity (Ekeanyanwu and Njoku 2014) and osteoarthritis healing effects (Choudhary et al 2014) offering potential benefits for human health (Ekeanyanwu and Njoku 2014) .…”

Role of EtMIC4 EGF-like in regulating the apoptosis of Eimeria tenella host cells via the EGFR pathway

“…After autophosphorylation, EGFR directly binds or acts indirectly on the GRB2 complex to activate the Ras protein. The activated Ras activates the downstream serine/threonine protein kinase, and Raf can phosphorylates ERK-1/2 ( Chen et al, 2021 ).…”