Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism
Abstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy du...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202002404 |
| _version_ | 1818941812945977344 |
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| author | Yi Ding Jie Yu Xingyu Chen Shaoyun Wang Zhaoxu Tu Guangxia Shen Huixue Wang Renbing Jia Shengfang Ge Jing Ruan Kam W. Leong Xianqun Fan |
| author_facet | Yi Ding Jie Yu Xingyu Chen Shaoyun Wang Zhaoxu Tu Guangxia Shen Huixue Wang Renbing Jia Shengfang Ge Jing Ruan Kam W. Leong Xianqun Fan |
| author_sort | Yi Ding |
| collection | DOAJ |
| description | Abstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose‐dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL−1, Cdot‐induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL−1, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25–100 µg mL−1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS‐producing nanoparticles in tumor imaging and therapy. |
| first_indexed | 2024-12-20T07:01:30Z |
| format | Article |
| id | doaj.art-3b71c81a88134e3daa693b56469029bd |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-20T07:01:30Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-3b71c81a88134e3daa693b56469029bd2022-12-21T19:49:11ZengWileyAdvanced Science2198-38442021-04-0188n/an/a10.1002/advs.202002404Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine MetabolismYi Ding0Jie Yu1Xingyu Chen2Shaoyun Wang3Zhaoxu Tu4Guangxia Shen5Huixue Wang6Renbing Jia7Shengfang Ge8Jing Ruan9Kam W. Leong10Xianqun Fan11Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Biomedical Engineering Columbia University New York NY 10027 USAState Key Laboratory of Oncogenes and Related Genes Institute for Personalized Medicine School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaDepartment of Biomedical Engineering Columbia University New York NY 10027 USADepartment of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 ChinaAbstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose‐dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL−1, Cdot‐induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL−1, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25–100 µg mL−1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS‐producing nanoparticles in tumor imaging and therapy.https://doi.org/10.1002/advs.202002404glutaminemetabolomicsmTORROSuveal melanoma |
| spellingShingle | Yi Ding Jie Yu Xingyu Chen Shaoyun Wang Zhaoxu Tu Guangxia Shen Huixue Wang Renbing Jia Shengfang Ge Jing Ruan Kam W. Leong Xianqun Fan Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism Advanced Science glutamine metabolomics mTOR ROS uveal melanoma |
| title | Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism |
| title_full | Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism |
| title_fullStr | Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism |
| title_full_unstemmed | Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism |
| title_short | Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism |
| title_sort | dose dependent carbon dot induced ros promote uveal melanoma cell tumorigenicity via activation of mtor signaling and glutamine metabolism |
| topic | glutamine metabolomics mTOR ROS uveal melanoma |
| url | https://doi.org/10.1002/advs.202002404 |
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