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Int J Mol Sci. 2014 Apr 3;15(4):5680-98. doi: 10.3390/ijms15045680.

LXXLL peptide converts transportan 10 to a potent inducer of apoptosis in breast cancer cells.

Author information

1
Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia. kairit@protobios.com.
2
Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia. madis@protobios.com.
3
Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia. tom@protobios.com.
4
Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia. kaia@protobios.com.

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.

PMID:
24705462
PMCID:
PMC4013589
DOI:
10.3390/ijms15045680
[Indexed for MEDLINE]
Free PMC Article
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