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The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer

Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast canc...

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Autores principales: Fan, Chen, Wang, Yijie, Huang, Hui, Li, Wenzhen, Ma, Jialin, Yao, Dongping, Tang, Zijun, Xue, Taixiong, Ha, Liyang, Ren, Yan, Zhang, Yiwen, Wang, Qin, Xie, Yongmei, Luo, Yi, Tan, Rui, Gu, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099110/
https://www.ncbi.nlm.nih.gov/pubmed/33967793
http://dx.doi.org/10.3389/fphar.2021.651976
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author Fan, Chen
Wang, Yijie
Huang, Hui
Li, Wenzhen
Ma, Jialin
Yao, Dongping
Tang, Zijun
Xue, Taixiong
Ha, Liyang
Ren, Yan
Zhang, Yiwen
Wang, Qin
Xie, Yongmei
Luo, Yi
Tan, Rui
Gu, Jian
author_facet Fan, Chen
Wang, Yijie
Huang, Hui
Li, Wenzhen
Ma, Jialin
Yao, Dongping
Tang, Zijun
Xue, Taixiong
Ha, Liyang
Ren, Yan
Zhang, Yiwen
Wang, Qin
Xie, Yongmei
Luo, Yi
Tan, Rui
Gu, Jian
author_sort Fan, Chen
collection PubMed
description Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The in vitro results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer.
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spelling pubmed-80991102021-05-06 The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer Fan, Chen Wang, Yijie Huang, Hui Li, Wenzhen Ma, Jialin Yao, Dongping Tang, Zijun Xue, Taixiong Ha, Liyang Ren, Yan Zhang, Yiwen Wang, Qin Xie, Yongmei Luo, Yi Tan, Rui Gu, Jian Front Pharmacol Pharmacology Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The in vitro results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8099110/ /pubmed/33967793 http://dx.doi.org/10.3389/fphar.2021.651976 Text en Copyright © 2021 Fan, Wang, Huang, Li, Ma, Yao, Tang, Xue, Ha, Ren, Zhang, Wang, Xie, Luo, Tan and Gu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Fan, Chen
Wang, Yijie
Huang, Hui
Li, Wenzhen
Ma, Jialin
Yao, Dongping
Tang, Zijun
Xue, Taixiong
Ha, Liyang
Ren, Yan
Zhang, Yiwen
Wang, Qin
Xie, Yongmei
Luo, Yi
Tan, Rui
Gu, Jian
The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title_full The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title_fullStr The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title_full_unstemmed The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title_short The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer
title_sort tetramethylpyrazine derivative statmp-151: a novel small molecule stat3 inhibitor with promising activity against breast cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099110/
https://www.ncbi.nlm.nih.gov/pubmed/33967793
http://dx.doi.org/10.3389/fphar.2021.651976
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