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Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling
PURPOSE: This research aims to investigate the intervention and mechanism of 50% acetone extract of C. officinalis leaves (SZYY) on melanoma xenografts. PATIENTS AND METHODS: Tumor size and cardiac function were measured via ultrasound. The accumulation of 2-deoxy-D-glucose (2-DG) in tumor tissue wa...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169088/ https://www.ncbi.nlm.nih.gov/pubmed/34093025 http://dx.doi.org/10.2147/OTT.S308371 |
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author | Xu, Ruiqi Zeng, Mengnan Wu, Yuanyuan Wang, Shengchao Zhang, Beibei Zhang, Jingke Kan, Yuxuan Li, Benke Cao, Bing Zheng, Xiaoke Feng, Weisheng |
author_facet | Xu, Ruiqi Zeng, Mengnan Wu, Yuanyuan Wang, Shengchao Zhang, Beibei Zhang, Jingke Kan, Yuxuan Li, Benke Cao, Bing Zheng, Xiaoke Feng, Weisheng |
author_sort | Xu, Ruiqi |
collection | PubMed |
description | PURPOSE: This research aims to investigate the intervention and mechanism of 50% acetone extract of C. officinalis leaves (SZYY) on melanoma xenografts. PATIENTS AND METHODS: Tumor size and cardiac function were measured via ultrasound. The accumulation of 2-deoxy-D-glucose (2-DG) in tumor tissue was examined with near-infrared in vivo imaging. Flow cytometry was performed to assess apoptosis and reactive oxygen species (ROS) levels in tumor and immune cells in spleen. The levels of inflammatory cytokines in serum were detected by cytometric bead array. The expression of proliferation-, apoptosis-, and angiogenesis-related proteins in tumor cells was measured to evaluate the underlying mechanisms. Subsequently, the effects of four compounds separated from SZYY on the proliferation and migration of A375 cells and STAT3 signaling were examined. The peak identification and contents of the four components were performed via high-performance liquid chromatography (HPLC). Finally, we evaluated the inhibitory effects of STAT3 overexpression on the cytotoxic activity of four constituents in A375 cells. RESULTS: SZYY inhibited the growth and glycolysis of melanoma xenograft in mice, improved cardiac function, increased the percentages of macrophages, neutrophils, and lymphocytes in spleen, reduced the levels of IL-6, IL-17A, TNF-α, and IFN-γ in serum, promoted apoptosis and oxidative stress in tumor tissues, and inhibited STAT3 phosphorylation and expression of angiogenic factors. Chemical analysis showed that SZYY is rich in loganin, rutin, triohimas C, and triohimas D, which all could restrain the proliferation and migration of A375 cells and inhibit the phosphorylation and nuclear translocation of STAT3. Moreover, STAT3 overexpression could diminish the cytotoxic activity of four compounds on A375 cells. CONCLUSION: SZYY could exert anti-melanoma effects via inhibiting STAT3 signaling to induce apoptosis and inhibit tumor angiogenesis. Its active ingredients might be loganin, rutin, triohimas C, and triohimas D. |
format | Online Article Text |
id | pubmed-8169088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-81690882021-06-03 Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling Xu, Ruiqi Zeng, Mengnan Wu, Yuanyuan Wang, Shengchao Zhang, Beibei Zhang, Jingke Kan, Yuxuan Li, Benke Cao, Bing Zheng, Xiaoke Feng, Weisheng Onco Targets Ther Original Research PURPOSE: This research aims to investigate the intervention and mechanism of 50% acetone extract of C. officinalis leaves (SZYY) on melanoma xenografts. PATIENTS AND METHODS: Tumor size and cardiac function were measured via ultrasound. The accumulation of 2-deoxy-D-glucose (2-DG) in tumor tissue was examined with near-infrared in vivo imaging. Flow cytometry was performed to assess apoptosis and reactive oxygen species (ROS) levels in tumor and immune cells in spleen. The levels of inflammatory cytokines in serum were detected by cytometric bead array. The expression of proliferation-, apoptosis-, and angiogenesis-related proteins in tumor cells was measured to evaluate the underlying mechanisms. Subsequently, the effects of four compounds separated from SZYY on the proliferation and migration of A375 cells and STAT3 signaling were examined. The peak identification and contents of the four components were performed via high-performance liquid chromatography (HPLC). Finally, we evaluated the inhibitory effects of STAT3 overexpression on the cytotoxic activity of four constituents in A375 cells. RESULTS: SZYY inhibited the growth and glycolysis of melanoma xenograft in mice, improved cardiac function, increased the percentages of macrophages, neutrophils, and lymphocytes in spleen, reduced the levels of IL-6, IL-17A, TNF-α, and IFN-γ in serum, promoted apoptosis and oxidative stress in tumor tissues, and inhibited STAT3 phosphorylation and expression of angiogenic factors. Chemical analysis showed that SZYY is rich in loganin, rutin, triohimas C, and triohimas D, which all could restrain the proliferation and migration of A375 cells and inhibit the phosphorylation and nuclear translocation of STAT3. Moreover, STAT3 overexpression could diminish the cytotoxic activity of four compounds on A375 cells. CONCLUSION: SZYY could exert anti-melanoma effects via inhibiting STAT3 signaling to induce apoptosis and inhibit tumor angiogenesis. Its active ingredients might be loganin, rutin, triohimas C, and triohimas D. Dove 2021-05-28 /pmc/articles/PMC8169088/ /pubmed/34093025 http://dx.doi.org/10.2147/OTT.S308371 Text en © 2021 Xu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Xu, Ruiqi Zeng, Mengnan Wu, Yuanyuan Wang, Shengchao Zhang, Beibei Zhang, Jingke Kan, Yuxuan Li, Benke Cao, Bing Zheng, Xiaoke Feng, Weisheng Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title | Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title_full | Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title_fullStr | Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title_full_unstemmed | Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title_short | Acetone Extract of Cornus officinalis Leaves Exerts Anti-Melanoma Effects via Inhibiting STAT3 Signaling |
title_sort | acetone extract of cornus officinalis leaves exerts anti-melanoma effects via inhibiting stat3 signaling |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169088/ https://www.ncbi.nlm.nih.gov/pubmed/34093025 http://dx.doi.org/10.2147/OTT.S308371 |
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