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 μM 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.
Department of Internal Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
Simona
S
D'Aguanno
Igea
I
D'Agnano
Michele
M
De Canio
Claudia
C
Rossi
Sergio
S
Bernardini
Giorgio
G
Federici
Andrea
A
Urbani
D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019295:Computational Biology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005069:Evaluation Studies as Topic; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D009447:Neuroblastoma / Q000378:metabolism*; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results; D054875:Ubiquitination
D000970:Antineoplastic Agents; D020543:Proteome; D017382:Reactive Oxygen Species; D003474:Curcumin; D002945:Cisplatin