Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents
7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1014854/full |
| _version_ | 1828295855803727872 |
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| author | Chao Yang Chao Yang Chao Yang An-Jie Xia Cheng-Hao Du Ming-Xing Hu You-Ling Gong Rong Tian Xin Jiang Yong-Mei Xie |
| author_facet | Chao Yang Chao Yang Chao Yang An-Jie Xia Cheng-Hao Du Ming-Xing Hu You-Ling Gong Rong Tian Xin Jiang Yong-Mei Xie |
| author_sort | Chao Yang |
| collection | DOAJ |
| description | 7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo. These results suggested that 5b could be a promising drug candidate for treating colorectal cancer. |
| first_indexed | 2024-04-13T12:02:05Z |
| format | Article |
| id | doaj.art-e29381d4fc0a44f2bb2a31f7f93c545e |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T12:02:05Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e29381d4fc0a44f2bb2a31f7f93c545e2022-12-22T02:47:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10148541014854Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agentsChao Yang0Chao Yang1Chao Yang2An-Jie Xia3Cheng-Hao Du4Ming-Xing Hu5You-Ling Gong6Rong Tian7Xin Jiang8Yong-Mei Xie9State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, ChinaCognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University Medical College, Shenzhen, Guangdong, ChinaDepartment of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, ChinaDepartment of Biological Sciences, USC Dana and David Dornsife College of Letters, Arts and Sciences, Los Angeles, CA, United StatesState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, ChinaDepartment of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo. These results suggested that 5b could be a promising drug candidate for treating colorectal cancer.https://www.frontiersin.org/articles/10.3389/fphar.2022.1014854/fullwarburg effect7-ethyl-10-hydroxycamptothecinglucose conjugatescolorectal canceranticancer |
| spellingShingle | Chao Yang Chao Yang Chao Yang An-Jie Xia Cheng-Hao Du Ming-Xing Hu You-Ling Gong Rong Tian Xin Jiang Yong-Mei Xie Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents Frontiers in Pharmacology warburg effect 7-ethyl-10-hydroxycamptothecin glucose conjugates colorectal cancer anticancer |
| title | Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents |
| title_full | Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents |
| title_fullStr | Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents |
| title_full_unstemmed | Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents |
| title_short | Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents |
| title_sort | discovery of highly potent and selective 7 ethyl 10 hydroxycamptothecin glucose conjugates as potential anti colorectal cancer agents |
| topic | warburg effect 7-ethyl-10-hydroxycamptothecin glucose conjugates colorectal cancer anticancer |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1014854/full |
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