2. Academic Validation
  3. Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate attenuates the malignant biological behaviors of non-small cell lung cancer via suppressing EGFR/PI3K/AKT/mTOR signaling pathway

Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate attenuates the malignant biological behaviors of non-small cell lung cancer via suppressing EGFR/PI3K/AKT/mTOR signaling pathway

  • J Pharm Pharmacol. 2024 Jan 18:rgae008. doi: 10.1093/jpp/rgae008.
Liyi Zou 1,  Xiaodan Li 1 2,  Jiansuo Lin 3,  Xuehong Fang 4,  Jie Lin 1,  Lu Zhang 5,  Yan Zhang 1,  Yanwen Liang 5,  Jianwei Ren 6 7,  Yi Liu 5,  Zunnan Huang 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, China.
  • 2 Department of Pharmacy, People's Hospital of Longhua District, Shenzhen, Guangdong 518109, China.
  • 3 Department of Physiology, College of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong 523808, China.
  • 4 Department of Pharmacy, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City, Shenzhen, Guangdong 518172, China.
  • 5 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
  • 6 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR 999077, China.
  • 7 Shenzhen Ritzcon Biological Technology Co., Ltd., Shenzhen, Guangdong 518108, China.
PMID: 38241189 DOI: 10.1093/jpp/rgae008
Abstract

Objective: The goal of the study is to examine the impact on the malignant biological behaviors of non-small cell lung Cancer (NSCLC) of a novel coumarin derivative, ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate (C2F). It also aims to define its underlying mechanism.

Methods: NSCLC cell lines and xenograft nude mice model were conducted to explore the anti-NSCLC effects of C2F in vitro and in vivo. Then, network pharmacology analysis and molecular docking were applied to estimate the possible targets of C2F in NSCLC. Finally, the underlying mechanism of C2F against NSCLC cellular proliferation and tumor development was confirmed using inhibitors or activators of the PI3K/Akt signaling pathway.

Results: Our results showed that C2F was able to inhibit proliferation, migration, and invasion of NSCLC cell lines, induce cell cycle arrest and Apoptosis in vitro, and prevent tumor growth in vivo. In addition, the estimated glomerular filtration rate and its downstream pathway (PI3K/Akt/mTOR) were found to be critical for the anti-NSCLC activity of C2F.

Conclusions: C2F inhibits malignant biological behaviors of NSCLC by suppressing EGFR/PI3K/Akt/mTOR signaling pathway.

Keywords

EGFR; PI3K/AKT/mTOR; ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate; malignant biological behaviors; non-small cell lung cancer.

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