Label-free quantitative proteomics of the MCF-7 cellular response to a ferritin–metallodrug complex†
Auoxo3 is a gold(III) compound endowed with cytotoxic activity towards a variety of malignant cells. Encapsulation of Auoxo3 within horse spleen ferritin (Ft) improves the selectivity of the gold compound towards cancer cells over normal cells. In the current work, the changes in protein expression are presented in response to MCF-7 stimulation with Auoxo3-encapsulated Ft versus the free Au(III) compound by a label-free proteomics approach. A 159-protein dataset showed significant changes between the stimulations with Auoxo3 and Auoxo3-encapsulated Ft, suggesting that this cellular perturbation caused the alteration of different cellular processes. In detail, roughly 30% of proteins were downregulated mainly in the spliceosome complex (U2AF1, SF3B2, PRPF4, SNSRP200, EFTUD2, PRPF6, and PRPF8) in agreement with the cytostatic effect observed during cellular growth. Another 30% of proteins were upregulated primarily in glutathione biosynthesis, suggesting an alteration of the redox potential, as validated by Western blot analyses. To the best of our knowledge, this work represents the first large scale proteomics study on the effects of a gold-based drug encapsulated within the Ft nanocage on cancer cells.