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,* email, 1,2email, 1email and 1,3,* email
Received: 23 January 2014; in revised form: 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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

Tints K, Prink M, Neuman T, Palm K. LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells. International Journal of Molecular Sciences. 2014; 15(4):5680-5698.

Chicago/Turabian Style

Tints, Kairit; Prink, Madis; Neuman, Toomas; Palm, Kaia. 2014. "LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells." Int. J. Mol. Sci. 15, no. 4: 5680-5698.


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