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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Main Authors: Yanfang Sun, Yi Gu, Xiaoyan Gao, Xiaoyan Jin, Michael Wink, Farukh S. Sharopov, Linjun Yang, Gautam Sethi
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Pharmacological Research
Subjects:
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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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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