Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway
BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity.
METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis.
RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth.
CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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Enthalten in: |
Aging - 15(2023), 16 vom: 28. Aug., Seite 8258-8274 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Qi, Yufeng [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 07.09.2023 Date Revised 30.09.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.18632/aging.204967 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM361492030 |
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245 | 1 | 0 | |a Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway |
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520 | |a BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity | ||
520 | |a METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis | ||
520 | |a RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth | ||
520 | |a CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
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700 | 1 | |a Wu, Haodong |e verfasserin |4 aut | |
700 | 1 | |a Zhu, Tianru |e verfasserin |4 aut | |
700 | 1 | |a Liu, Zitian |e verfasserin |4 aut | |
700 | 1 | |a Liu, Conghui |e verfasserin |4 aut | |
700 | 1 | |a Yan, Congzhi |e verfasserin |4 aut | |
700 | 1 | |a Wu, Zhixuan |e verfasserin |4 aut | |
700 | 1 | |a Xu, Yiying |e verfasserin |4 aut | |
700 | 1 | |a Bai, Ying |e verfasserin |4 aut | |
700 | 1 | |a Yang, Lehe |e verfasserin |4 aut | |
700 | 1 | |a Cheng, Dezhi |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Xiaohua |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Haiyang |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Chengguang |e verfasserin |4 aut | |
700 | 1 | |a Dai, Xuanxuan |e verfasserin |4 aut | |
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