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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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