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Int. J. Mol. Sci. 2014, 15(4), 5680-5698; doi:10.3390/ijms15045680
Article

LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells

1,* , 1,2
,
1
 and
1,3,*
1 Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia 2 Competence Centre for Cancer Research, Akadeemia tee 15, Tallinn 12618, Estonia 3 Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia
* Authors to whom correspondence should be addressed.
Received: 23 January 2014 / Revised: 18 March 2014 / Accepted: 24 March 2014 / Published: 3 April 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

Degenerate expression of transcription coregulator proteins is observed in most human cancers. Therefore, in targeted anti-cancer therapy development, intervention at the level of cancer-specific transcription is of high interest. The steroid receptor coactivator-1 (SRC-1) is highly expressed in breast, endometrial, and prostate cancer. It is present in various transcription complexes, including those containing nuclear hormone receptors. We examined the effects of a peptide that contains the LXXLL-motif of the human SRC-1 nuclear receptor box 1 linked to the cell-penetrating transportan 10 (TP10), hereafter referred to as TP10-SRC1LXXLL, on proliferation and estrogen-mediated transcription of breast cancer cells in vitro. Our data show that TP10-SRC1LXXLL induced dose-dependent cell death of breast cancer cells, and that this effect was not affected by estrogen receptor (ER) status. Surprisingly TP10-SRC1LXXLL severely reduced the viability and proliferation of hormone-unresponsive breast cancer MDA-MB-231 cells. In addition, the regulation of the endogenous ERα direct target gene pS2 was not affected by TP10-SRC1LXXLL in estrogen-stimulated MCF-7 cells. Dermal fibroblasts were similarly affected by treatment with higher concentrations of TP10-SRC1LXXLL and this effect was significantly delayed. These results suggest that the TP10-SRC1LXXLL peptide may be an effective drug candidate in the treatment of cancers with minimal therapeutic options, for example ER-negative tumors.
Keywords: SRC-1; LXXLL; cancer; cell penetrating peptide SRC-1; LXXLL; cancer; cell penetrating peptide
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Tints, K.; Prink, M.; Neuman, T.; Palm, K. LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells. Int. J. Mol. Sci. 2014, 15, 5680-5698.

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