Original ArticlesTheophylline administration markedly reduces hepatic and pulmonary implantation of B16-F10 melanoma cells in miceLentini, A.; Vidal-Vanaclocha, F.; Facchiano, F.; Caraglia, M.; Abbruzzese, A.; Beninati, S.*Author Information Department of Biology, University ‘Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy. Tel: (+39) 6 72594350; Fax: (+39) 6 2023500; Email: [email protected] (A. Lentini, S. Beninati). Department of Cellular Biology and Morphological Sciences, University of the Basque Country, Leioa, Vizcaya, Spain (F. Vidal-Vanaclocha). Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, Rome, Italy (F. Facchiano). Department of Biochemistry and Biophysics, University of Naples, Italy (M. Caraglia, A. Abbruzzese). *To whom correspondence should be addressed Received 7 March 2000; accepted in revised form 3 May 2000 Melanoma Research: October 2000 - Volume 10 - Issue 5 - p 435-443 Buy Abstract Theophylline-treated B16-F10 melanoma cells show a lower experimental metastatic potentialin vivo. To identify the possible mechanism(s) involved and on the basis of previous reports, we tested the induction of apoptosis in B16-F10 cells. Fluorescence activated cell sorter (FACS) analysis and p53 overexpression in theophylline-treated B16-F10 melanoma cells appeared to suggest enhanced cell death by apoptosis. Thein vivoeffects of orally administered theophylline in mice were investigated using different treatment schedules in mice that had undergone hepatic or pulmonary colonization with tumour cells. Mice received theophylline in their drinking water according to different protocols: (i) from 3 days before tumour cell inoculation until animal sacrifice (`early treatment'); (ii) from 3 days before until 3 days after tumour cell inoculation (`short treatment'); or (iii) from 3 days after tumour cell inoculation until animal sacrifice (`late treatment'). In the ‘early treatment’ group, the number of melanoma foci was reduced by 92.3% in the liver and 81.4% in the lung compared with control animals (P< 0.001). In the ‘short treatment’ group, there was an 80.2% and 72.2% reduction in liver and lung metastases, respectively (P< 0.001). In the ‘late treatment’ group, the inhibition of metastasis was 59.7% for liver and 45.3% for lung (P< 0.005). Survival studies showed that 50% of the ‘early’ theophylline-treated animals died 33.2 ± 2.0 days after intrasplenic injection (control group: 23.1 ± 1.8 days;P< 0.001) and 33.9 ± 2.5 days after tail vein injection (control group: 24.1 ± 1.4 days;P< 0.001). Taken together, these observations provide useful information for the potential clinical application of theophylline as a chemotherapeutic agent against malignant melanoma. © 2000 Lippincott Williams & Wilkins, Inc.