title: p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells.
abstract: Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. Electronic address: concettina.cappadone@unibo.it.
authors.forename: C
authors.initials: C
authors.lastname: Cappadone
authors.affiliation: Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Stefanelli
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Malucelli
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Onofrillo
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Locatelli
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rambaldi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sargenti
authors.affiliation: ELETTRA-Sincrotrone Trieste S.C.p.A., Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Merolle
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Roma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Farruggia
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Graziadio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Montanaro
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Iotti
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007211:Indoles; C000604478:NSC743420; D034741:RNA, Small Interfering; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D000469:Alkaline Phosphatase
keywords: Apoptosis; Indole derivative; Osteosarcoma; SaOS2; U2OS; p53