Shotgun proteomics and network analysis of neuroblastoma cell lines treated with curcumin

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 mM 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 ubiquitin-proteasome system may be the main way through which curcumin
performs its multi-target activity.