A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-08-10

AUTHORS

Irina Nayvelt, Shali John, Hui-Chen Hsu, PingAr Yang, Wensheng Liu, Gokul Das, Mervi T. Hyvönen, Leena Alhonen, Tuomo A. Keinänen, Akira Shirahata, Rajesh Patel, Thresia Thomas, T. J. Thomas

ABSTRACT

BE-3-3-3-3 (1,15-(ethylamino)4,8,12-triazapentadecane) is a bis(ethyl)polyamine analogue under investigation as a therapeutic agent for breast cancer. Since estradiol (E2) is a critical regulatory molecule in the growth of breast cancer, we examined the effect of BE-3-3-3-3 on estrogen receptor α (ERα) positive MCF-7 cells in the presence and absence of E2. In the presence of E2, a concentration-dependent decrease in DNA synthesis was observed using [3H]-thymidine incorporation assay. In the absence of E2, low concentrations (2.5–10 μM) of BE-3-3-3-3 increased [3H]-thymidine incorporation at 24 and 48 h. BE-3-3-3-3 induced the expression of early response genes, c-myc and c-fos, in the absence of E2, but not in its presence, as determined by real-time quantitative polymerase chain reaction (qPCR). BE-3-3-3-3 had no significant effect on these genes in an ERα-negative cell line, MDA-MB-231. Chromatin immunoprecipitation assay demonstrated enhanced promoter occupation by either E2 or BE-3-3-3-3 of an estrogen-responsive gene pS2/Tff1 by ERα and its co-activator, steroid receptor co-activator 3 (SRC-3). Confocal microscopy of BE-3-3-3-3-treated cells revealed membrane localization of ERα, similar to that induced by E2. The failure of BE-3-3-3-3 to inhibit cell proliferation was associated with autophagic vacuole formation, and the induction of Beclin 1 and MAP LC3 II. These results indicate a differential effect of BE-3-3-3-3 on MCF-7 cells in the absence and presence of E2, and suggest that pre-clinical and clinical development of polyamine analogues might require special precautions and selection of sensitive subpopulation of patients. More... »

PAGES

899-911

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  • Journal

    TITLE

    Amino Acids

    ISSUE

    2-3

    VOLUME

    42

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00726-011-1005-0

    DOI

    http://dx.doi.org/10.1007/s00726-011-1005-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1049807246

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21830120


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