Shotgun proteomics and network analysis of neuroblastoma cell lines treated with curcuminPresented, in part, at the 6th Annual National Conference of the Italian Proteomics Association held in Turin, 21st24th June 2011.Electronic supplementary information (ESI) available. See DOI: 10.1039/c2mb05498a

Curcumin is a natural compound with recognized anti-inflammatory properties, but its anticancer activity is still object of study. We provided an unsupervised molecular investigation of the main proteome rearrangements involved in the cellular response to curcumin in a human neuroblastoma cell line sensitive to cisplatin and its resistant counterpart by a comparative proteomic approach. Shotgun analysis demonstrated that 66 proteins were differentially expressed in response to 24 h treatment with 40 M curcumin in sensitive cells, whereas 32 proteins were significantly modulated in treated resistant cells. Functional analysis revealed that proteins involved in cellular assembly and organization, biosynthesis and glycolysis were down-regulated by curcumin treatment. Proteome changes were associated to cell cycle arrest in the G2/M phase and accumulation of polyubiquitinated proteins, also confirmed by flow cytometry and immunoblotting analysis, but not to a significant increment of reactive oxygen species production. Since the polyubiquitination of proteins influences a wide range of cellular pathways, the inhibition of the ubiquitinproteasome system may be the main way through which curcumin performs its multi-target activity. Unsupervised molecular investigation of proteome changes highlighted cell cycle arrest in the G2/M phase and accumulation of polyubiquitinated proteins in a neuroblastoma cell line sensitive to cisplatin and its resistant counterpart after curcumin treatment.