The novel compound Austocystin R induces cycle arrest and autophagy in triple-negative breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway
- VernacularTitle:新化合物Austocystin R通过调控PI3K/AKT/mTOR信号通路诱导三阴性乳腺癌细胞周期阻滞和自噬
- Author:
Xin-yue GONG
1
;
Min WEI
1
;
Xiao-qin YU
1
;
Yun-lei XU
1
;
Yi-fan BAI
1
;
Cheng-xiong LIU
1
;
Fan CHENG
1
;
Kun ZOU
1
;
Jian-feng CHEN
1
Author Information
- Publication Type:Journal Article
- Keywords: Austocystin R; Eupatorium chinense; TN-BC; PI3K/AKT/mTOR signaling pathway; cell cycle arrest; autophagy
- From: Chinese Pharmacological Bulletin 2025;41(9):1651-1658
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.
