title: High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222.
abstract: The biological activity of a combined treatment of U251, U373 and T98G glioma cell lines with two anti-miR PNAs, directed against miR‑221 and miR‑222 and conjugated with an ocataarginine tail (R8-PNA-a221 and R8-PNA-a222) for efficient cellular delivery, was determined. Apoptosis was analyzed, and the effect of the combined treatment of glioma cells with either or both PNAs on the reversion of drug-resistance phenotype was assessed in the temozolomide-resistant T98G glioma cell line. Selectivity of PNA/miRNA interactions was studied by surface plasmon resonance (SPR)-based Biacore analysis. Specificity of the PNA effects at the cellular level was analyzed by RT-qPCR. These experiments support the concept that the effects of R8-PNA-a221 and R8-PNA-a222 are specific. The studies on apoptosis confirmed that the R8-PNA-a221 induces apoptosis and demonstrated the pro-apoptotic effects of R8-PNA-a222. Remarkably, increased pro-apoptotic effects were obtained with the co-administration of both anti-miR‑221 and anti-miR‑222 PNAs. In addition, co-administration of R8-PNA-a221 and R8-PNA-a222 induced apoptosis of TMZ-treated T98G cells at a level higher than that obtained following singular administration of R8-PNA-a221 or R8-PNA-a222.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Montagner
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gasparello
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Manicardi
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Corradini
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Breveglieri
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Milani
authors.affiliation: Laboratory of Molecular Pathology, University-Hospital of Verona, Verona, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Dechecchi
authors.affiliation: Laboratory of Molecular Pathology, University-Hospital of Verona, Verona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020135:Peptide Nucleic Acids / Q000737:chemistry; D010641:Phenotype; D020349:Surface Plasmon Resonance; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D035683:MicroRNAs; D020135:Peptide Nucleic Acids; D000077204:Temozolomide; C525709:MIR221, human; C525710:MIR222, human