8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells
Colorectal cancer (CRC) is one of the most common malignant tumors with a high lethal rate globally, and novel strategies for its prevention and therapy are urgently needed. In our previous work, 8-methoxyflindersine (8-MF), a quinoline alkaloid, was isolated from the Dictamni cortex, and its bioact...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Dianbao Zhang Yunmei Fu Ying Liu Yifan Wu Jiayu Chen Luting Zhang Rui Wang Zaixing Chen Tao Liu |
| author_facet | Dianbao Zhang Yunmei Fu Ying Liu Yifan Wu Jiayu Chen Luting Zhang Rui Wang Zaixing Chen Tao Liu |
| author_sort | Dianbao Zhang |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is one of the most common malignant tumors with a high lethal rate globally, and novel strategies for its prevention and therapy are urgently needed. In our previous work, 8-methoxyflindersine (8-MF), a quinoline alkaloid, was isolated from the Dictamni cortex, and its bioactivities were largely unknown. In this study, we found that 8-MF significantly inhibited cell viability in the CRC cell lines LoVo and RKO. The 8-MF-induced CRC cell apoptosis, as well as cell cycle disorder, were further verified by cyclins dysregulation in mRNA and protein levels. Further, the activation of MAPK family members p38 and ERK1/2 was observed after 8-MF treatment. Moreover, the protein–protein interaction of 8-MF with cyclins and MAPKs was demonstrated using the STRING database. The 8-MF could bind to p38 and ERK1/2 proteins in molecular docking. Taken together, we found that 8-MF induced apoptosis and cell cycle disorder involving MAPK signaling activation in CRC cells, indicating 8-MF as a novel lead compound candidate for the development of anti-tumor drugs for CRC. |
| first_indexed | 2024-03-11T04:17:29Z |
| format | Article |
| id | doaj.art-c6943b216e5749009e90039476af84d1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:17:29Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
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| spelling | doaj.art-c6943b216e5749009e90039476af84d12023-11-17T23:04:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249803910.3390/ijms240980398-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer CellsDianbao Zhang0Yunmei Fu1Ying Liu2Yifan Wu3Jiayu Chen4Luting Zhang5Rui Wang6Zaixing Chen7Tao Liu8Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, ChinaDepartment of Natural Products Chemistry, School of Pharmacy, China Medical University, Shenyang 110122, ChinaDepartment of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, ChinaDepartment of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, ChinaDepartment of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, ChinaDepartment of Natural Products Chemistry, School of Pharmacy, China Medical University, Shenyang 110122, ChinaDepartment of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, ChinaCentral Laboratory, School of Pharmacy, China Medical University, Shenyang 110122, ChinaDepartment of Natural Products Chemistry, School of Pharmacy, China Medical University, Shenyang 110122, ChinaColorectal cancer (CRC) is one of the most common malignant tumors with a high lethal rate globally, and novel strategies for its prevention and therapy are urgently needed. In our previous work, 8-methoxyflindersine (8-MF), a quinoline alkaloid, was isolated from the Dictamni cortex, and its bioactivities were largely unknown. In this study, we found that 8-MF significantly inhibited cell viability in the CRC cell lines LoVo and RKO. The 8-MF-induced CRC cell apoptosis, as well as cell cycle disorder, were further verified by cyclins dysregulation in mRNA and protein levels. Further, the activation of MAPK family members p38 and ERK1/2 was observed after 8-MF treatment. Moreover, the protein–protein interaction of 8-MF with cyclins and MAPKs was demonstrated using the STRING database. The 8-MF could bind to p38 and ERK1/2 proteins in molecular docking. Taken together, we found that 8-MF induced apoptosis and cell cycle disorder involving MAPK signaling activation in CRC cells, indicating 8-MF as a novel lead compound candidate for the development of anti-tumor drugs for CRC.https://www.mdpi.com/1422-0067/24/9/80398-methoxyflindersinecolorectal cancerapoptosiscell cycleMAPK signaling |
| spellingShingle | Dianbao Zhang Yunmei Fu Ying Liu Yifan Wu Jiayu Chen Luting Zhang Rui Wang Zaixing Chen Tao Liu 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells International Journal of Molecular Sciences 8-methoxyflindersine colorectal cancer apoptosis cell cycle MAPK signaling |
| title | 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells |
| title_full | 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells |
| title_fullStr | 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells |
| title_full_unstemmed | 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells |
| title_short | 8-Methoxyflindersine-Induced Apoptosis and Cell Cycle Disorder Involving MAPK Signaling Activation in Human Colorectal Cancer Cells |
| title_sort | 8 methoxyflindersine induced apoptosis and cell cycle disorder involving mapk signaling activation in human colorectal cancer cells |
| topic | 8-methoxyflindersine colorectal cancer apoptosis cell cycle MAPK signaling |
| url | https://www.mdpi.com/1422-0067/24/9/8039 |
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