LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells
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 bre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/15/4/5680 |
| _version_ | 1798044885597552640 |
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| author | Kairit Tints Madis Prink Toomas Neuman Kaia Palm |
| author_facet | Kairit Tints Madis Prink Toomas Neuman Kaia Palm |
| author_sort | Kairit Tints |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:11:30Z |
| format | Article |
| id | doaj.art-ed0b75663a964339ac65edf915a46832 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-11T23:11:30Z |
| publishDate | 2014-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ed0b75663a964339ac65edf915a468322022-12-22T03:57:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-04-011545680569810.3390/ijms15045680ijms15045680LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer CellsKairit Tints0Madis Prink1Toomas Neuman2Kaia Palm3Protobios LLC, Mäealuse 4, Tallinn 12618, EstoniaProtobios LLC, Mäealuse 4, Tallinn 12618, EstoniaProtobios LLC, Mäealuse 4, Tallinn 12618, EstoniaProtobios LLC, Mäealuse 4, Tallinn 12618, EstoniaDegenerate 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.http://www.mdpi.com/1422-0067/15/4/5680SRC-1LXXLLcancercell penetrating peptide |
| spellingShingle | Kairit Tints Madis Prink Toomas Neuman Kaia Palm LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells International Journal of Molecular Sciences SRC-1 LXXLL cancer cell penetrating peptide |
| title | LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells |
| title_full | LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells |
| title_fullStr | LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells |
| title_full_unstemmed | LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells |
| title_short | LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells |
| title_sort | lxxll peptide converts transportan 10 to a potent inducer of apoptosis in breast cancer cells |
| topic | SRC-1 LXXLL cancer cell penetrating peptide |
| url | http://www.mdpi.com/1422-0067/15/4/5680 |
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