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

作　　者：Ruijie Xu Zhijie Yao Hao Zhang Haitao Li Wei Chen 

机构地区：[1]State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,China [2]School of Food Science and Technology,Jiangnan University,Wuxi 214122,China

出　　处：《Food Science and Human Wellness》2024年第4期2221-2233,共13页食品科学与人类健康（英文）

基　　金：supported by the National Natural Science Foundation of China (81773064,31972973,32021005);National Youth 1000 Talents Plan;the Jiangsu Specially-Appointed Professor Program;Jiangsu 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

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 A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA_(2)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.TXA_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)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.

关 键 词：APIGENIN ANOIKIS Breast cancer metastasis Thromboxane A2 

分 类 号：TS201.4[轻工技术与工程—食品科学] R737.9[轻工技术与工程—食品科学与工程]