Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis
Abstract Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi‐targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202201541 |
| _version_ | 1798019905909424128 |
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| author | Jiawei Huo Jie Li Yang Liu Libin Yang Xinran Cao Chong Zhao Yicheng Lu Wei Zhou Shumu Li Jianan Liu Jiao Li Xing Li Jing Wan Rui Wen Mingming Zhen Chunru Wang Chunli Bai |
| author_facet | Jiawei Huo Jie Li Yang Liu Libin Yang Xinran Cao Chong Zhao Yicheng Lu Wei Zhou Shumu Li Jianan Liu Jiao Li Xing Li Jing Wan Rui Wen Mingming Zhen Chunru Wang Chunli Bai |
| author_sort | Jiawei Huo |
| collection | DOAJ |
| description | Abstract Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi‐targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC‐4, TAPC‐3, and TCPC‐4. TAPC‐4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC‐4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC‐4 to heat shock protein Hsp90‐beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti‐tumor drug development. |
| first_indexed | 2024-04-11T16:48:58Z |
| format | Article |
| id | doaj.art-79466b15b82445eda9a16b0e46e58c80 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T16:48:58Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-79466b15b82445eda9a16b0e46e58c802022-12-22T04:13:30ZengWileyAdvanced Science2198-38442022-10-01929n/an/a10.1002/advs.202201541Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and MetastasisJiawei Huo0Jie Li1Yang Liu2Libin Yang3Xinran Cao4Chong Zhao5Yicheng Lu6Wei Zhou7Shumu Li8Jianan Liu9Jiao Li10Xing Li11Jing Wan12Rui Wen13Mingming Zhen14Chunru Wang15Chunli Bai16Beijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaSchool of Pharmacy Guizhou Medical University Guian New District Guizhou 550025 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaAbstract Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi‐targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC‐4, TAPC‐3, and TCPC‐4. TAPC‐4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC‐4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC‐4 to heat shock protein Hsp90‐beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti‐tumor drug development.https://doi.org/10.1002/advs.202201541amphipathic aminated [60]fullerenecell cycle arrestcell mobility suppressionmesenchymal–epithelial transitionprotein target |
| spellingShingle | Jiawei Huo Jie Li Yang Liu Libin Yang Xinran Cao Chong Zhao Yicheng Lu Wei Zhou Shumu Li Jianan Liu Jiao Li Xing Li Jing Wan Rui Wen Mingming Zhen Chunru Wang Chunli Bai Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis Advanced Science amphipathic aminated [60]fullerene cell cycle arrest cell mobility suppression mesenchymal–epithelial transition protein target |
| title | Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis |
| title_full | Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis |
| title_fullStr | Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis |
| title_full_unstemmed | Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis |
| title_short | Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis |
| title_sort | amphiphilic aminated derivatives of 60 fullerene as potent inhibitors of tumor growth and metastasis |
| topic | amphipathic aminated [60]fullerene cell cycle arrest cell mobility suppression mesenchymal–epithelial transition protein target |
| url | https://doi.org/10.1002/advs.202201541 |
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