Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling
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 anal...
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Elsevier
2023-09-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661823002220 |
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author | Yanfang Sun Yi Gu Xiaoyan Gao Xiaoyan Jin Michael Wink Farukh S. Sharopov Linjun Yang Gautam Sethi |
author_facet | Yanfang Sun Yi Gu Xiaoyan Gao Xiaoyan Jin Michael Wink Farukh S. Sharopov Linjun Yang Gautam Sethi |
author_sort | Yanfang Sun |
collection | DOAJ |
description | 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 μM and 7.76 ± 1.16 μM, 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 β-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. |
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issn | 1096-1186 |
language | English |
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spelling | doaj.art-759a9c5011e5487fa02159e37825380c2023-09-09T04:54:31ZengElsevierPharmacological Research1096-11862023-09-01195106866Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signalingYanfang Sun0Yi Gu1Xiaoyan Gao2Xiaoyan Jin3Michael Wink4Farukh S. Sharopov5Linjun Yang6Gautam Sethi7College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 928, No.2 Street, Qiantang District, Hangzhou 310018, China; Corresponding authors.College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 928, No.2 Street, Qiantang District, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, 928, No.2 Street, Qiantang District, Hangzhou 310018, ChinaDepartment of Surgical Oncology, Zhejiang Taizhou Municipal Hospital, No. 218, Hengjie Road, Taizhou 318020, ChinaInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 329, Heidelberg 69120, GermanyResearch Institution ''Chinese-Tajik Innovation Center for Natural Products'', National Academy of Sciences of Tajikistan, No. 267, Айнй Road, Dushanbe 734025, TajikistanDepartment of Surgical Oncology, Zhejiang Taizhou Municipal Hospital, No. 218, Hengjie Road, Taizhou 318020, China; Corresponding authors.Department of Pharmacology, National University of Singapore, NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore, 117600, Singapore.; Corresponding authors.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 μM and 7.76 ± 1.16 μM, 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 β-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.http://www.sciencedirect.com/science/article/pii/S1043661823002220Lycorine (PubChem CID:72378)Breast carcinomaWnt/β-catenin signaling pathwayEpithelial to mesenchymal transitionTumor-bearing mice model |
spellingShingle | Yanfang Sun Yi Gu Xiaoyan Gao Xiaoyan Jin Michael Wink Farukh S. Sharopov Linjun Yang Gautam Sethi Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling Pharmacological Research Lycorine (PubChem CID:72378) Breast carcinoma Wnt/β-catenin signaling pathway Epithelial to mesenchymal transition Tumor-bearing mice model |
title | Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling |
title_full | Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling |
title_fullStr | Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling |
title_full_unstemmed | Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling |
title_short | Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β-catenin signaling |
title_sort | lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and β catenin signaling |
topic | Lycorine (PubChem CID:72378) Breast carcinoma Wnt/β-catenin signaling pathway Epithelial to mesenchymal transition Tumor-bearing mice model |
url | http://www.sciencedirect.com/science/article/pii/S1043661823002220 |
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