title: Preclinical evaluation of the antineoplastic efficacy of 7-(2-hydroxyethyl)theophylline on melanoma cancer cells.
abstract: Differentiation-based therapeutics are an underutilized but potentially a significant option for cancer treatment. The effect of methylxanthines on melanoma cell differentiation has been well documented. We report the in-vitro and in-vivo anticancer potential of a theophylline analogue, 7-(2-hydroxyethyl)theophylline (HET), on murine B16-F10 and human Sk-Mel 110 metastatic melanoma cell lines. The effects on cell proliferation were related to the induction of differentiation, demonstrated as increased intracellular transglutaminase activity. The involvement of this methylxanthine in the control of the in-vitro adhesion and in the in-vivo metastastic spread of melanoma cells was further investigated. HET oral administration of C57BL6/N mice intravenously injected with B16-F10 cells markedly reduced lung metastases frequency. The overall results demonstrated that HET possesses a remarkable in-vivo antimetastatic capability.
authors.affiliation: Department of Biology, University of Rome, Tor Vergata, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lentini
authors.forename: Claudio
authors.initials: C
authors.lastname: Tabolacci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nardi
authors.forename: Palma
authors.initials: P
authors.lastname: Mattioli
authors.forename: Bruno
authors.initials: B
authors.lastname: Provenzano
authors.forename: Simone
authors.initials: S
authors.lastname: Beninati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D013806:Theophylline; D011503:Transglutaminases; C008749:etofylline