Chrysin Inhibits TAMs-Mediated Autophagy Activation Via CDK1/ULK1 Pathway and Reverses TAMs-Mediated Growth-Promoting Effects in Non-Small Cell Lung Cancer

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Apr 27

PMID 38675475

Authors

Xinglinzi Tang

Xiaoru Luo

Xiao Wang

Yi Zhang

Jiajia Xie

Xuan Niu

Xiaopeng Lu

Xi Deng

Zheng Xu

Fanwei Wu

Affiliations

Soon will be listed here.

Abstract

The natural flavonoid compound chrysin has promising anti-tumor effects. In this study, we aimed to investigate the mechanism by which chrysin inhibits the growth of non-small cell lung cancer (NSCLC). Through in vitro cell culture and animal models, we explored the impact of chrysin on the growth of NSCLC cells and the pro-cancer effects of tumor-associated macrophages (TAMs) and their mechanisms. We observed that M2-TAMs significantly promoted the growth and migration of NSCLC cells, while also markedly activating the autophagy level of these cells. Chrysin displayed a significant inhibitory effect on the growth of NSCLC cells, and it could also suppress the pro-cancer effects of M2-TAMs and inhibit their mediated autophagy. Furthermore, combining network pharmacology, we found that chrysin inhibited TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 signaling pathway, rather than the classical mTOR/ULK1 signaling pathway. Our study reveals a novel mechanism by which chrysin inhibits TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 pathway, thereby suppressing NSCLC growth. This discovery not only provides new therapeutic strategies for NSCLC but also opens up new avenues for further research on chrysin.

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