title: Distinct cellular responses induced by saporin and a transferrin-saporin conjugate in two different human glioblastoma cell lines.
abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of ~12-18 months post-diagnosis. GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4-Pseudomonas aeruginosa exotoxin A (IL4-PE, NBI-3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha-TP-38, IL13-PE38, and a transferrin-C diphtheriae toxin mutant (Tf-CRM107). In this work, we studied the effects of the plant ribosome-inactivating saporin and of its chimera transferrin-saporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways.
authors.affiliation: Department of Basic and Applied Biology, University of L'Aquila, L'Aquila, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cimini
authors.forename: S
authors.initials: S
authors.lastname: Mei
authors.forename: E
authors.initials: E
authors.lastname: Benedetti
authors.forename: G
authors.initials: G
authors.lastname: Laurenti
authors.forename: I
authors.initials: I
authors.lastname: Koutris
authors.forename: B
authors.initials: B
authors.lastname: Cinque
authors.forename: M G
authors.initials: MG
authors.lastname: Cifone
authors.forename: R
authors.initials: R
authors.lastname: Galzio
authors.forename: G
authors.initials: G
authors.lastname: Pitari
authors.forename: L
authors.initials: L
authors.lastname: Di Leandro
authors.forename: F
authors.initials: F
authors.lastname: Giansanti
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: M S
authors.initials: MS
authors.lastname: Fabbrini
authors.forename: R
authors.initials: R
authors.lastname: Ippoliti
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic / Q000379:methods; D015195:Drug Design; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058726:Nanoconjugates / Q000633:toxicity; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics / Q000633:toxicity*; D000076985:Saporins; D014168:Transferrin / Q000235:genetics / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D058726:Nanoconjugates; D054789:Ribosome Inactivating Proteins, Type 1; D014168:Transferrin; D016159:Tumor Suppressor Protein p53; D000076985:Saporins