Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation
Breast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I (DHT), a bioactive compound in <i>Salvia miltiorrhiza</i> Bunge (<i>S. miltiorrhiza</i>), has inhibitory effect...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15180 |
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| author | Huan Zhao Yi Liang Chengtao Sun Yufei Zhai Xuan Li Mi Jiang Ruiwen Yang Xiaojuan Li Qijin Shu Guoyin Kai Bing Han |
| author_facet | Huan Zhao Yi Liang Chengtao Sun Yufei Zhai Xuan Li Mi Jiang Ruiwen Yang Xiaojuan Li Qijin Shu Guoyin Kai Bing Han |
| author_sort | Huan Zhao |
| collection | DOAJ |
| description | Breast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I (DHT), a bioactive compound in <i>Salvia miltiorrhiza</i> Bunge (<i>S. miltiorrhiza</i>), has inhibitory effects on numerous cancers. Here, we investigated the anti-metastatic effect of DHT on BC, where DHT more strongly inhibited the growth of BC cells (MDA-MB-231, 4T1, MCF-7, and SKBR-3) than breast epithelial cells (MCF-10a). Additionally, DHT repressed the wound healing, invasion, and migration activities of 4T1 cells. In the 4T1 spontaneous metastasis model, DHT (20 mg/kg) blocked metastasis progression and distribution in the lung tissue by 74.9%. DHT reversed the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate, as well as ameliorated NETs-induced metastasis. Furthermore, it inhibited Ly6G<sup>+</sup>Mpo<sup>+</sup> neutrophils infiltration and H3Cit expression in the lung tissues. RNA sequencing, western blot, and bioinformatical analysis indicated that <i>TIMP1</i> could modulate DHT acting on lung metastasis inhibition. The study demonstrated a novel suppression mechanism of DHT on NETs formation to inhibit BC metastasis. |
| first_indexed | 2024-03-09T17:44:08Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0379f3c5852242fb9ce9e03197f305d82023-11-24T11:14:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231518010.3390/ijms232315180Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps FormationHuan Zhao0Yi Liang1Chengtao Sun2Yufei Zhai3Xuan Li4Mi Jiang5Ruiwen Yang6Xiaojuan Li7Qijin Shu8Guoyin Kai9Bing Han10Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaDepartment of Oncology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaDepartment of Oncology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaLaboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou 310053, ChinaBreast cancer (BC) is a common female malignancy, worldwide. BC death is predominantly caused by lung metastasis. According to previous studies, Dihydrotanshinone I (DHT), a bioactive compound in <i>Salvia miltiorrhiza</i> Bunge (<i>S. miltiorrhiza</i>), has inhibitory effects on numerous cancers. Here, we investigated the anti-metastatic effect of DHT on BC, where DHT more strongly inhibited the growth of BC cells (MDA-MB-231, 4T1, MCF-7, and SKBR-3) than breast epithelial cells (MCF-10a). Additionally, DHT repressed the wound healing, invasion, and migration activities of 4T1 cells. In the 4T1 spontaneous metastasis model, DHT (20 mg/kg) blocked metastasis progression and distribution in the lung tissue by 74.9%. DHT reversed the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate, as well as ameliorated NETs-induced metastasis. Furthermore, it inhibited Ly6G<sup>+</sup>Mpo<sup>+</sup> neutrophils infiltration and H3Cit expression in the lung tissues. RNA sequencing, western blot, and bioinformatical analysis indicated that <i>TIMP1</i> could modulate DHT acting on lung metastasis inhibition. The study demonstrated a novel suppression mechanism of DHT on NETs formation to inhibit BC metastasis.https://www.mdpi.com/1422-0067/23/23/15180breast cancerlung metastasisdihydrotanshinone Ineutrophil extracellular trapsRNA sequencing<i>TIMP1</i> |
| spellingShingle | Huan Zhao Yi Liang Chengtao Sun Yufei Zhai Xuan Li Mi Jiang Ruiwen Yang Xiaojuan Li Qijin Shu Guoyin Kai Bing Han Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation International Journal of Molecular Sciences breast cancer lung metastasis dihydrotanshinone I neutrophil extracellular traps RNA sequencing <i>TIMP1</i> |
| title | Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation |
| title_full | Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation |
| title_fullStr | Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation |
| title_full_unstemmed | Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation |
| title_short | Dihydrotanshinone I Inhibits the Lung Metastasis of Breast Cancer by Suppressing Neutrophil Extracellular Traps Formation |
| title_sort | dihydrotanshinone i inhibits the lung metastasis of breast cancer by suppressing neutrophil extracellular traps formation |
| topic | breast cancer lung metastasis dihydrotanshinone I neutrophil extracellular traps RNA sequencing <i>TIMP1</i> |
| url | https://www.mdpi.com/1422-0067/23/23/15180 |
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