Journal
ACS APPLIED BIO MATERIALS
Volume 3, Issue 2, Pages 977-985Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.9b01001
Keywords
fullerenol; cytotoxicity; autophagy; lysosomal dysfunction; starvation
Funding
- National Natural Science Foundation of China [21473125]
- National Special Subject of Infectious Diseases [2018ZX10301405]
- Guangxi Science and Technology Project [GuiKeAD17195081]
- Bagui Scholar Program of Guangxi Province
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Autophagy is well-known as a common cellular response to nanomaterials. As one of the most comprehensively studied carbon-based nanomaterials, fullerene and its derivatives have been reported to bring about autophagic features in various cell lines, but little is known about the role of fullerenol (C-60(OH)(44)) on the modulation of autophagy in human gastric tumor cell line SGC-7901. Fullerenol treatment led to the accumulation of autophagosomes, as evidenced by the increased fluorescent intensity of monodansylcadaverine (MDC) staining cells, an elevated level of LC3 protein, and the observation of auotphagosomes in cytoplasm. Subsequent results of the p62 level demonstrated that the accumulation of autophagosomes resulted from the blockade of autophagic flux rather than the activation of autophagy. Fullerenol disrupted autophagic flux by impairing lysosomal function, including lysosome membrane permeabilization (LMP), alkaline of lysosomes, and reduced activity of capthesin B. Interestingly, fullerenol treatment was noncytotoxic under a nutrient-rich condition. When serum was deprived, cytotoxicity occurred in a concentration- and time-dependent manner, along with massive vacuoles in cytoplasm, a large amount of ROS generation, and finally cell death, which can be ascribed to the disruption of essential autophagy in cells. Taken together, understanding this autophagy-lysosome pathway will shed light on the potential anticancer application of fullerenol.
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