Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling

被引:7
作者
Sun, Yanfang [1 ]
Gu, Yi [1 ]
Gao, Xiaoyan [1 ]
Jin, Xiaoyan [2 ]
Wink, Michael [3 ]
Sharopov, Farukh S. [4 ]
Yang, Linjun [2 ]
Sethi, Gautam [5 ]
机构
[1] Zhejiang Sci Tech Univ, Coll Life Sci & Med, 928, 2 St, Hangzhou 310018, Peoples R China
[2] Zhejiang Taizhou Municipal Hosp, Dept Surg Oncol, 218, Hengjie Rd, Taizhou 318020, Peoples R China
[3] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Neuenheimer Feld 329, D-69120 Heidelberg, Germany
[4] Natl Acad Sci Tajikistan, Res Inst Chinese, Tajik Innovat Ctr Nat Prod, 267, Anhn Rd, Dushanbe 734025, Tajikistan
[5] Natl Univ Singapore, NUS Ctr Canc Res, Yong Loo Lin Sch Med, 16 Med Dr, Singapore 117600, Singapore
基金
中国国家自然科学基金;
关键词
Lycorine (PubChem CID:72378); Breast carcinoma; Wnt/beta-catenin signaling pathway; Epithelial to mesenchymal transition; Tumor-bearing mice model; CANCER; METASTASIS; PROTEINS; GROWTH; ACTIN;
D O I
10.1016/j.phrs.2023.106866
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Lycorine, an isoquinoline alkaloid can exhibit significant anti-cancer effects. The present study was conducted to illustrate the underlying mechanisms of action of lycorine on breast carcinoma under in vitro and in vivo settings Tandem Mass Tag assay and Kyoto Encyclopedia of Genes and Genomes analysis revealed that 20 signaling pathways were closely related to tumorigenesis, especially Wnt signaling pathway and tight junctions. The results demonstrated that lycorine evidently inhibited the proliferation of MDA-MB-231 and MCF-7 cells with IC50 values of 1.84 +/- 0.21 mu M and 7.76 +/- 1.16 mu M, respectively. It also blocked cell cycle in G2/M phase, caused a decrease in mitochondrial membrane potential, and induced apoptosis pathways through regulating caspase-3, caspase-8, caspase-9, and PARP expression. Moreover, lycorine effectively repressed the beta-catenin signaling and reversed epithelial-mesenchymal transition (EMT) process. Furthermore, 4T1/Luc homograft tumor model was used to further demonstrate that lycorine significantly inhibited the growth and metastasis of breast tumor. These findings highlight the significance of lycorine as potential anti-neoplastic agent to combat breast cancer.
引用
收藏
页数:13
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