Effects of a bis(benzyl)spermine analog on MCF-7 breast cancer cells in culture and nude mice xenografts

  • Authors:
    • T Thomas
    • N Shah
    • C Faaland
    • M Gallo
    • E Yurkow
    • P Satyaswaroop
  • View Affiliations

  • Published online on: January 1, 1997     https://doi.org/10.3892/or.4.1.5
  • Pages: 5-13
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Abstract

We studied the effects of a polyamine analog, N,N'-bis{3-[(phenylmethyl)amino]propyl}-1,7-diaminoheptane (MDL 27695) on MCF-7 cells, as part of an attempt to develop new drugs for breast cancer treatment. Using [H-3]-thymidine incorporation assay and long-term growth curves, we found that MDL 27695 inhibited the growth of MCF-7 cells in a dose-dependent manner in the low mu M range. G1 synchronized cells progressing in cell cycle showed delayed and inefficient entry into S phase in the presence of 4 mu M MDL 27695. Consistent with a G1 arrest, MDL 27695 significantly reduced estradiol-mediated increase in the expression of cyclin D1. HPLC analysis showed that treatment of MCF-7 cells with MDL 27695 reduced the accumulation of natural polyamines, putrescine, spermidine, and spermine, by 43, 38, and 45%, respectively, at 8 h after the initiation of cell cycle. This decrease in polyamine levels was not associated with a decrease in the activity of polyamine biosynthetic (ornithine decarboxylase, ODC; s-adenosylmethionine decarboxylase, SAMDC) or catabolizing (spermidine/spermine acetyltransferase, SSAT) enzymes. However, there was a 40% decrease in the uptake of putrescine and spermidine, in cells treated with MDL 27695. Our studies also showed that MDL 27695, at a dose of 20 mg/kg, caused a significant inhibition of tumor growth in nude mice harboring MCF-7 cell derived tumors, without overt symptoms of toxicity. These data indicate that the polyamine analog MDL 27695 is an efficient inhibitor of MCF-7 breast cancer cell growth in vitro and in vivo. Our results suggest that polyamines are critical factors in cell cycle regulation of breast cancer cells and potential targets for therapy.

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January 1997
Volume 4 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Thomas T, Shah N, Faaland C, Gallo M, Yurkow E and Satyaswaroop P: Effects of a bis(benzyl)spermine analog on MCF-7 breast cancer cells in culture and nude mice xenografts. Oncol Rep 4: 5-13, 1997.
APA
Thomas, T., Shah, N., Faaland, C., Gallo, M., Yurkow, E., & Satyaswaroop, P. (1997). Effects of a bis(benzyl)spermine analog on MCF-7 breast cancer cells in culture and nude mice xenografts. Oncology Reports, 4, 5-13. https://doi.org/10.3892/or.4.1.5
MLA
Thomas, T., Shah, N., Faaland, C., Gallo, M., Yurkow, E., Satyaswaroop, P."Effects of a bis(benzyl)spermine analog on MCF-7 breast cancer cells in culture and nude mice xenografts". Oncology Reports 4.1 (1997): 5-13.
Chicago
Thomas, T., Shah, N., Faaland, C., Gallo, M., Yurkow, E., Satyaswaroop, P."Effects of a bis(benzyl)spermine analog on MCF-7 breast cancer cells in culture and nude mice xenografts". Oncology Reports 4, no. 1 (1997): 5-13. https://doi.org/10.3892/or.4.1.5