Nanosize aminated fullerene for autophagic flux activation and G0/G1 phase arrest in cancer cells via post-transcriptional regulation
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Chunru Wang1(
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Functional fullerene derivatives exhibit special inhibitory effects on tumor progress and metastasis via diverse tumor microenvironment regulations, while the elusive molecular mechanisms hinder their clinical transformation. Herein, it is initially revealed that nanosize aminated fullerene (C70-EDA) can activate autophagic flux, induce G0/G1 cell cycle arrest to abrogate cancer cell proliferation, and significantly inhibit tumor growth in vivo. Mechanismly, C70-EDA promotes the expression of cathepsin D involved in autophagic activation via post-transcriptional regulation, attributing to the interaction with a panel of RNA binding proteins. The accumulation of cathepsin D induces the autophagic degradation of cyclin D1, which arouses G0/G1 phase arrest. This work unveils the fantastic anti-tumor activity of aminated fullerene, elucidates the molecular mechanism, and provides a new strategy for the antineoplastic drug development on functional fullerenes.
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Nanosize aminated fullerene for autophagic flux activation and G0/G1 phase arrest in cancer cells via post-transcriptional regulation
), Chunru Wang1(
)
Abstract
Functional fullerene derivatives exhibit special inhibitory effects on tumor progress and metastasis via diverse tumor microenvironment regulations, while the elusive molecular mechanisms hinder their clinical transformation. Herein, it is initially revealed that nanosize aminated fullerene (C70-EDA) can activate autophagic flux, induce G0/G1 cell cycle arrest to abrogate cancer cell proliferation, and significantly inhibit tumor growth in vivo. Mechanismly, C70-EDA promotes the expression of cathepsin D involved in autophagic activation via post-transcriptional regulation, attributing to the interaction with a panel of RNA binding proteins. The accumulation of cathepsin D induces the autophagic degradation of cyclin D1, which arouses G0/G1 phase arrest. This work unveils the fantastic anti-tumor activity of aminated fullerene, elucidates the molecular mechanism, and provides a new strategy for the antineoplastic drug development on functional fullerenes.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 51802310). All animal experiments were conducted according to protocols approved by the Institutional Animal Care and Use Committee in the Institute of Chemistry, Chinese Academy of Sciences. We also thank Shuo Xiao (Thermo Fisher Scientific) for the flow cytometry support.
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