Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein
BackgroundTriple-negative breast cancer is a common malignant tumor with unfavorable prognosis affecting women worldwide; thus, there is an urgent need for novel therapeutic drugs with improved anti-tumor activity. Rac family small GTPase 1 (Rac1) plays an important role in malignant behavior and is...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00754/full |
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| author | Xinxiao Li Yunfeng Liu Yuhua Zhao Wei Tian Lina Zhai Huifeng Pang Jiankang Kang Huaxin Hou Yanhua Chen Danrong Li Danrong Li |
| author_facet | Xinxiao Li Yunfeng Liu Yuhua Zhao Wei Tian Lina Zhai Huifeng Pang Jiankang Kang Huaxin Hou Yanhua Chen Danrong Li Danrong Li |
| author_sort | Xinxiao Li |
| collection | DOAJ |
| description | BackgroundTriple-negative breast cancer is a common malignant tumor with unfavorable prognosis affecting women worldwide; thus, there is an urgent need for novel therapeutic drugs with improved anti-tumor activity. Rac family small GTPase 1 (Rac1) plays an important role in malignant behavior and is a promising therapeutic target. We reported an anthraquinone compound, Rhein, and its derivative, 4F, and investigated their downregulation effects on Rac1 in breast cancer cells in vitro.MethodsThe inhibition of cell proliferation by derivative 4F was investigated in two breast cancer (MDA-MB-231 and MCF-7) and normal breast (MCF-10A) cell lines by cell counting kit-8 assay and growth curves. The role of 4F in cell migration and invasion and cytoskeletal change were assessed by Transwell chamber assay and F-actin staining, respectively. The affinity of Rhein and its derivative for Rac1 protein and the regulation of Rac1 promoter activity were evaluated by molecular docking software and luciferase reporter gene assay, respectively. Rac1 protein expression was determined by western blot assay.ResultsCompared to Rhein, derivative 4F more strongly inhibited breast cancer cell proliferation, migration, and invasion and also cause cytoskeletal changes like those in paclitaxel. Derivative 4F not only bound more stably to Rac1 but also inhibited Rac1 promoter activity in cells and downregulated Rac1 protein expression.ConclusionsRhein derivative 4F is a new anthraquinone compound with better anti-tumor activity than that of the lead compound Rhein in breast cancer. It down-regulated Rac1 expression and may be a small molecule inhibitor of Rac1. |
| first_indexed | 2024-12-22T12:57:09Z |
| format | Article |
| id | doaj.art-2f9c7128976d47ae9b96609c8273d3a3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T12:57:09Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2f9c7128976d47ae9b96609c8273d3a32022-12-21T18:25:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00754528190Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 ProteinXinxiao Li0Yunfeng Liu1Yuhua Zhao2Wei Tian3Lina Zhai4Huifeng Pang5Jiankang Kang6Huaxin Hou7Yanhua Chen8Danrong Li9Danrong Li10Department of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaCollege of Pharmacy, Guangxi Medical University, Nanning, ChinaLife Sciences Institute, Guangxi Medical University, Nanning, ChinaDepartment of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaLife Sciences Institute, Guangxi Medical University, Nanning, ChinaCollege of Pharmacy, Guangxi Medical University, Nanning, ChinaDepartment of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Basic Research, Guangxi Medical University Cancer Hospital, Nanning, ChinaLife Sciences Institute, Guangxi Medical University, Nanning, ChinaBackgroundTriple-negative breast cancer is a common malignant tumor with unfavorable prognosis affecting women worldwide; thus, there is an urgent need for novel therapeutic drugs with improved anti-tumor activity. Rac family small GTPase 1 (Rac1) plays an important role in malignant behavior and is a promising therapeutic target. We reported an anthraquinone compound, Rhein, and its derivative, 4F, and investigated their downregulation effects on Rac1 in breast cancer cells in vitro.MethodsThe inhibition of cell proliferation by derivative 4F was investigated in two breast cancer (MDA-MB-231 and MCF-7) and normal breast (MCF-10A) cell lines by cell counting kit-8 assay and growth curves. The role of 4F in cell migration and invasion and cytoskeletal change were assessed by Transwell chamber assay and F-actin staining, respectively. The affinity of Rhein and its derivative for Rac1 protein and the regulation of Rac1 promoter activity were evaluated by molecular docking software and luciferase reporter gene assay, respectively. Rac1 protein expression was determined by western blot assay.ResultsCompared to Rhein, derivative 4F more strongly inhibited breast cancer cell proliferation, migration, and invasion and also cause cytoskeletal changes like those in paclitaxel. Derivative 4F not only bound more stably to Rac1 but also inhibited Rac1 promoter activity in cells and downregulated Rac1 protein expression.ConclusionsRhein derivative 4F is a new anthraquinone compound with better anti-tumor activity than that of the lead compound Rhein in breast cancer. It down-regulated Rac1 expression and may be a small molecule inhibitor of Rac1.https://www.frontiersin.org/article/10.3389/fphar.2020.00754/fullRhein derivativedrug designRac family small GTPase 1breast canceranticancer |
| spellingShingle | Xinxiao Li Yunfeng Liu Yuhua Zhao Wei Tian Lina Zhai Huifeng Pang Jiankang Kang Huaxin Hou Yanhua Chen Danrong Li Danrong Li Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein Frontiers in Pharmacology Rhein derivative drug design Rac family small GTPase 1 breast cancer anticancer |
| title | Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein |
| title_full | Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein |
| title_fullStr | Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein |
| title_full_unstemmed | Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein |
| title_short | Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein |
| title_sort | rhein derivative 4f inhibits the malignant phenotype of breast cancer by downregulating rac1 protein |
| topic | Rhein derivative drug design Rac family small GTPase 1 breast cancer anticancer |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00754/full |
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