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
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

January 1997
Volume 4 Issue 1

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
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