A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.

  • Authors:
    • M L Cerutti
    • E D'Orio
    • L Davel
    • L Colombo
    • P Parma
    • M Diament
    • I Stillitani
    • M E Gelpi
    • S R Leicach
    • A M Eiján
  • View Affiliations

  • Published online on: March 1, 1999     https://doi.org/10.3892/ijo.14.3.585
  • Pages: 585-676
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Abstract

The design of more effective therapies for metastatic disease involves development of new compounds able to specifically block the malignant process. We demonstrated previously that a new synthetic nitrogenated compound 3'-1-chloroethyl-2,3-dihydro-1H-imidazo-(2, 1-i)-purine-4-ium-7-yl-3'-deoxy-1',5', 6'-tri-O-(methylsulfonyl)-muco-inositol chloride (DIC) had an anti-proliferative activity on tumor cells in vitro. In the present work we demonstrate that DIC induces apoptosis on the LM3 murine mammary adenocarcinoma cell line in vitro and has anti-angiogenic activity in vivo. We also evaluated toxicity, biodistribution and anti-neoplastic properties of DIC in vivo. Toxicity studies allowed us to establish the LD50 (750 mg/kg body weight). Administration of 250 mg/kg/day (LD10) for 6 days did not cause overt toxic effects. Biodistribution assays revealed that DIC was rapidly eliminated (60% at t=10 min), although it accumulated in tumor tissue at higher concentrations than in other tissues. Daily s.c. treatment with DIC (LD10) for 24 days significantly reduced the number of spontaneous lung metastases. These results suggest that DIC has the ability of impairing the metastatic development by inhibiting angiogenesis and inducing apoptosis on tumor cells.

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Mar 1999
Volume 14 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cerutti M, D'Orio E, Davel L, Colombo L, Parma P, Diament M, Stillitani I, Gelpi M, Leicach S, Eiján A, Eiján A, et al: A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.. Int J Oncol 14: 585-676, 1999.
APA
Cerutti, M., D'Orio, E., Davel, L., Colombo, L., Parma, P., Diament, M. ... Eiján, A. (1999). A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.. International Journal of Oncology, 14, 585-676. https://doi.org/10.3892/ijo.14.3.585
MLA
Cerutti, M., D'Orio, E., Davel, L., Colombo, L., Parma, P., Diament, M., Stillitani, I., Gelpi, M., Leicach, S., Eiján, A."A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.". International Journal of Oncology 14.3 (1999): 585-676.
Chicago
Cerutti, M., D'Orio, E., Davel, L., Colombo, L., Parma, P., Diament, M., Stillitani, I., Gelpi, M., Leicach, S., Eiján, A."A synthetic, nitrogenated antimetastatic and anti-angiogenic compound with low toxicity in vivo.". International Journal of Oncology 14, no. 3 (1999): 585-676. https://doi.org/10.3892/ijo.14.3.585