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Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway
BACKGROUND: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066752/ https://www.ncbi.nlm.nih.gov/pubmed/35505400 http://dx.doi.org/10.1186/s12906-022-03587-0 |
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author | Sheng, Dongya Zhao, Bei Zhu, Wenjing Wang, Tiantian Peng, Yu |
author_facet | Sheng, Dongya Zhao, Bei Zhu, Wenjing Wang, Tiantian Peng, Yu |
author_sort | Sheng, Dongya |
collection | PubMed |
description | BACKGROUND: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. MATERIALS AND METHODS: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. RESULTS: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. CONCLUSIONS: Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03587-0. |
format | Online Article Text |
id | pubmed-9066752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90667522022-05-04 Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway Sheng, Dongya Zhao, Bei Zhu, Wenjing Wang, Tiantian Peng, Yu BMC Complement Med Ther Research BACKGROUND: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. MATERIALS AND METHODS: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. RESULTS: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. CONCLUSIONS: Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03587-0. BioMed Central 2022-05-03 /pmc/articles/PMC9066752/ /pubmed/35505400 http://dx.doi.org/10.1186/s12906-022-03587-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sheng, Dongya Zhao, Bei Zhu, Wenjing Wang, Tiantian Peng, Yu Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title | Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title_full | Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title_fullStr | Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title_full_unstemmed | Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title_short | Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway |
title_sort | scutellaria barbata d.don (sbd) extracts suppressed tumor growth, metastasis and angiogenesis in prostate cancer via pi3k/akt pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066752/ https://www.ncbi.nlm.nih.gov/pubmed/35505400 http://dx.doi.org/10.1186/s12906-022-03587-0 |
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