Apigenin is an anoikis sensitizer with strong anti-metastatic properties in experimental breast cancer

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外文摘要：Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods.Among 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of celery.Phenotypically,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in mice.Mechanistically,we demonstrated that the thromboxane A2(TXA2)-TXA2 receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA2 signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer cells.TXA2 level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA2 biosynthesis in vitro and in vivo.Collectively,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.

外文关键词：

ApigeninAnoikisBreast cancer metastasisThromboxane A2

作者：

Ruijie Xu、Zhijie Yao、Hao Zhang、Haitao Li、Wei Chen

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作者单位：

State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,China

School of Food Science and Technology,Jiangnan University,Wuxi 214122,China

基金：

国家自然科学基金国家自然科学基金国家自然科学基金National Youth 1000 Talents Plan,the Jiangsu Specially-Appointed Professor ProgramJiangsu Province Recruitment Plan for High-level,Innovative and Entrepreneurial Talents(Innovative Research Team)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province

项目编号：

817730643197297332021005

出版年：

2024

DOI：

10.26599/FSHW.2022.9250185

食品科学与人类健康(英文)

CSTPCD

ISSN：

年,卷(期)：2024.13(4)

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