title: Metabolic Effects of Cobalt Ferrite Nanoparticles on Cervical Carcinoma Cells and Nontumorigenic Keratinocytes.
abstract: The cytotoxic response, cellular uptake, and metabolomic profile of HeLa and HaCaT cell lines treated with cobalt ferrite nanoparticles (CoFe2O4NPs) were investigated in this study. Cell viability assays showed low cytotoxicity caused by the uptake of the nanoparticles at 2 mg/mL. However, metabolomics revealed that these nanoparticles impacted cell metabolism even when tested at a concentration that presented low cytotoxicity according to the cell viability assay. The two cell lines shared stress-related metabolic changes such as increase in alanine and creatine levels. A reduced level of fumarate was also observed in HeLa cells after treatment with the nanoparticles, and this alteration can inhibit tumorigenesis. Fumarate is considered to be an oncometabolite that can inhibit prolyl hydroxylase, and this inhibition stabilizes HIF1α, one of the master regulators of tumorigenesis that promotes tumor growth and development. In summary, this study showed that nanoparticle-treated HeLa cells demonstrated decreased concentrations of metabolites associated with cell proliferation and tumor growth. The results clearly indicated that treatment with these nanoparticles might cause a perturbation in cellular metabolism.
authors.affiliation: Biology Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Ana Beatriz Bortolozo
authors.initials: AB
authors.lastname: Oliveira
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.|Multiuser Center for Biomolecular Innovation, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Fabio Rogério
authors.initials: FR
authors.lastname: de Moraes
authors.affiliation: Biology Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Natalia Maria
authors.initials: NM
authors.lastname: Candido
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sampaio
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Alex Silva
authors.initials: AS
authors.lastname: Paula
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: de Vasconcellos
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Thais Cerqueira
authors.initials: TC
authors.lastname: Silva
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Alex Henrique
authors.initials: AH
authors.lastname: Miller
authors.affiliation: Biology Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Rahal
authors.affiliation: Physics Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Jose Geraldo
authors.initials: JG
authors.lastname: Nery
authors.affiliation: Biology Department, São Paulo State University , São José do Rio Preto, 15054-000 São Paulo, Brazil.
authors.forename: Marilia Freitas
authors.initials: MF
authors.lastname: Calmon
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D005650:Fumarates / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D005650:Fumarates; C569492:cobalt ferrite; D003035:Cobalt
keywords: cell lines; cell uptake; cobalt ferrite nanoparticles; cytotoxicity; metabolomics