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Preclinical evaluation of the antineoplastic efficacy of 7-(2-hydroxyethyl)theophylline on melanoma cancer cells

Lentini, Alessandroa; Tabolacci, Claudioa; Nardi, Alessandrab; Mattioli, Palmaa; Provenzano, Brunoa; Beninati, Simonea

doi: 10.1097/CMR.0b013e328350d228

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.

Departments of aBiology

bMathematics, University of Rome, Tor Vergata, Rome, Italy

Correspondence to Simone Beninati, MD, Department of Biology, University Tor Vergata, Via della Ricerca Scientifica, Rome 00133, Italy Tel: +39 0672 594 228; fax: +39 0620 23500; e-mail:

Received April 12, 2011

Accepted December 28, 2011

© 2012 Lippincott Williams & Wilkins, Inc.