Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway
Colon cancer ranks among the most prevalent malignancies worldwide, trailing only lung and breast cancer in incidence. Despite the availability of numerous therapeutic strategies, the burden of new cases and fatalities remains high in countries undergoing socioeconomic transitions. Natural products...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224003536 |
| _version_ | 1797248440143446016 |
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| author | Qiushuang Wu Min Song Siyuan Luo Libin Guo Qingwen Zhang Hang Fai Kwok |
| author_facet | Qiushuang Wu Min Song Siyuan Luo Libin Guo Qingwen Zhang Hang Fai Kwok |
| author_sort | Qiushuang Wu |
| collection | DOAJ |
| description | Colon cancer ranks among the most prevalent malignancies worldwide, trailing only lung and breast cancer in incidence. Despite the availability of numerous therapeutic strategies, the burden of new cases and fatalities remains high in countries undergoing socioeconomic transitions. Natural products offer promising avenues for developing more effective and less toxic anticancer agents, expanding the clinical arsenal. In this investigation, we isolated a triterpenoid, (21 S,23 R,24 R)-21,23-epoxy-24-hydroxy-21-methoxytirucalla-7,25-dien-3-one (EHMT), from the fruits of Melia azedarach L., which exhibited significant inhibitory activity against colon cancer cells while sparing normal cells. EHMT effectively curtailed colony formation and induced apoptosis and cell cycle arrest in the HCT116 cell line. Furthermore, EHMT prompted the generation of reactive oxygen species (ROS) and the depolarization of mitochondrial membrane potential. Notably, EHMT treatment triggered ROS-mediated cell apoptosis via activation of the JNK signaling pathway in HCT116 cells. Additionally, our findings extended to Caenorhabditis elegans, where EHMT induced ROS accumulation and apoptosis. Collectively, these findings position EHMT as a promising candidate for the development of anticancer agents in the treatment of colon cancer, offering new hope in the battle against this formidable disease. |
| first_indexed | 2024-04-24T20:14:37Z |
| format | Article |
| id | doaj.art-c665f2ae9211437d86251a6023819203 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:14:37Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-c665f2ae9211437d86251a60238192032024-03-23T06:23:10ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-05-01174116469Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathwayQiushuang Wu0Min Song1Siyuan Luo2Libin Guo3Qingwen Zhang4Hang Fai Kwok5Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SARState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SARCancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SARCancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SARState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Corresponding author.Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Corresponding author at: Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR.Colon cancer ranks among the most prevalent malignancies worldwide, trailing only lung and breast cancer in incidence. Despite the availability of numerous therapeutic strategies, the burden of new cases and fatalities remains high in countries undergoing socioeconomic transitions. Natural products offer promising avenues for developing more effective and less toxic anticancer agents, expanding the clinical arsenal. In this investigation, we isolated a triterpenoid, (21 S,23 R,24 R)-21,23-epoxy-24-hydroxy-21-methoxytirucalla-7,25-dien-3-one (EHMT), from the fruits of Melia azedarach L., which exhibited significant inhibitory activity against colon cancer cells while sparing normal cells. EHMT effectively curtailed colony formation and induced apoptosis and cell cycle arrest in the HCT116 cell line. Furthermore, EHMT prompted the generation of reactive oxygen species (ROS) and the depolarization of mitochondrial membrane potential. Notably, EHMT treatment triggered ROS-mediated cell apoptosis via activation of the JNK signaling pathway in HCT116 cells. Additionally, our findings extended to Caenorhabditis elegans, where EHMT induced ROS accumulation and apoptosis. Collectively, these findings position EHMT as a promising candidate for the development of anticancer agents in the treatment of colon cancer, offering new hope in the battle against this formidable disease.http://www.sciencedirect.com/science/article/pii/S0753332224003536TriterpenoidApoptosisROSJNK pathwaysColon cancerNatural products |
| spellingShingle | Qiushuang Wu Min Song Siyuan Luo Libin Guo Qingwen Zhang Hang Fai Kwok Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway Biomedicine & Pharmacotherapy Triterpenoid Apoptosis ROS JNK pathways Colon cancer Natural products |
| title | Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway |
| title_full | Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway |
| title_fullStr | Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway |
| title_full_unstemmed | Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway |
| title_short | Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway |
| title_sort | unveil the mechanism for ehmt a novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ros mediated jnk signaling pathway |
| topic | Triterpenoid Apoptosis ROS JNK pathways Colon cancer Natural products |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224003536 |
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