A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells
Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU,...
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/13/3843 |
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| author | Weijia Zhang Chang Peng Xue Shen Yuemei Yuan Wei Zhang Chunjuan Yang Meicun Yao |
| author_facet | Weijia Zhang Chang Peng Xue Shen Yuemei Yuan Wei Zhang Chunjuan Yang Meicun Yao |
| author_sort | Weijia Zhang |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, <i>Sanguisorba officinalis</i> L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic. |
| first_indexed | 2024-03-10T10:06:45Z |
| format | Article |
| id | doaj.art-a5a2ded023804d1c90ffaefeffab19ca |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:06:45Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a5a2ded023804d1c90ffaefeffab19ca2023-11-22T01:31:39ZengMDPI AGMolecules1420-30492021-06-012613384310.3390/molecules26133843A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer CellsWeijia Zhang0Chang Peng1Xue Shen2Yuemei Yuan3Wei Zhang4Chunjuan Yang5Meicun Yao6School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Ecology, Sun Yat-sen University, 6# Ming De Yuan, Guangzhou University City, Guangzhou 510006, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau, ChinaDepartment of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy Harbin Medical University, Harbin 150081, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, ChinaColorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, <i>Sanguisorba officinalis</i> L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic.https://www.mdpi.com/1420-3049/26/13/3843colorectal cancerAGEapoptosisautophagyWnt/β-catenin signaling pathway |
| spellingShingle | Weijia Zhang Chang Peng Xue Shen Yuemei Yuan Wei Zhang Chunjuan Yang Meicun Yao A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells Molecules colorectal cancer AGE apoptosis autophagy Wnt/β-catenin signaling pathway |
| title | A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells |
| title_full | A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells |
| title_fullStr | A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells |
| title_full_unstemmed | A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells |
| title_short | A Bioactive Compound from <i>Sanguisorba officinalis</i> L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells |
| title_sort | bioactive compound from i sanguisorba officinalis i l inhibits cell proliferation and induces cell death in 5 fluorouracil sensitive resistant colorectal cancer cells |
| topic | colorectal cancer AGE apoptosis autophagy Wnt/β-catenin signaling pathway |
| url | https://www.mdpi.com/1420-3049/26/13/3843 |
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