A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems
The Wilms tumor protein 1 (WT1) transcription factor has been associated in malignant melanoma with cell survival and metastasis, thus emerging as a candidate for targeted therapy. A lysine–arginine rich peptide, WT1-pTj, derived from the ZF domain of WT1 was evaluated as an antitumor agent against...
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doaj-662503c711fb4c138eb788bb6790a70c2020-11-25T03:07:17ZengWileyFEBS Open Bio2211-54632014-01-014C15316110.1016/j.fob.2014.01.007A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systemsMariana H. MassaokaAlisson L. MatsuoCarlos R. FigueiredoNatalia GirolaCamyla F. FariaRicardo A. AzevedoLuiz R. TravassosThe Wilms tumor protein 1 (WT1) transcription factor has been associated in malignant melanoma with cell survival and metastasis, thus emerging as a candidate for targeted therapy. A lysine–arginine rich peptide, WT1-pTj, derived from the ZF domain of WT1 was evaluated as an antitumor agent against A2058 human melanoma cells and B16F10-Nex2 syngeneic murine melanoma. Peptide WT1-pTj quickly penetrated human melanoma cells and induced senescence, recognized by increased SA-β-galactosidase activity, enhanced transcriptional activity of p53, and induction of the cell cycle inhibitors p21 and p27. Moreover, the peptide bound to p53 and competed with WT1 protein for binding to p53. WT1-pTj treatment led to sustained cell growth suppression, abrogation of clonogenicity and G2/M cell cycle arrest. Notably, in vivo studies showed that WT1-pTj inhibited both the metastases and subcutaneous growth of murine melanoma in syngeneic mice, and prolonged the survival of nude mice challenged with human melanoma cells. The 27-amino acid cell-penetrating WT1-derived peptide, depends on C3 and H16 for effective antimelanoma activity, inhibits proliferation of WT1-expressing human tumor cell lines, and may have an effective role in the treatment of WT1-expressing malignancies.http://www.sciencedirect.com/science/article/pii/S2211546314000084Malignant melanomaWilms tumor 1 (WT1)Senescencep53 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mariana H. Massaoka Alisson L. Matsuo Carlos R. Figueiredo Natalia Girola Camyla F. Faria Ricardo A. Azevedo Luiz R. Travassos |
spellingShingle |
Mariana H. Massaoka Alisson L. Matsuo Carlos R. Figueiredo Natalia Girola Camyla F. Faria Ricardo A. Azevedo Luiz R. Travassos A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems FEBS Open Bio Malignant melanoma Wilms tumor 1 (WT1) Senescence p53 |
author_facet |
Mariana H. Massaoka Alisson L. Matsuo Carlos R. Figueiredo Natalia Girola Camyla F. Faria Ricardo A. Azevedo Luiz R. Travassos |
author_sort |
Mariana H. Massaoka |
title |
A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
title_short |
A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
title_full |
A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
title_fullStr |
A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
title_full_unstemmed |
A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
title_sort |
novel cell-penetrating peptide derived from wt1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems |
publisher |
Wiley |
series |
FEBS Open Bio |
issn |
2211-5463 |
publishDate |
2014-01-01 |
description |
The Wilms tumor protein 1 (WT1) transcription factor has been associated in malignant melanoma with cell survival and metastasis, thus emerging as a candidate for targeted therapy. A lysine–arginine rich peptide, WT1-pTj, derived from the ZF domain of WT1 was evaluated as an antitumor agent against A2058 human melanoma cells and B16F10-Nex2 syngeneic murine melanoma. Peptide WT1-pTj quickly penetrated human melanoma cells and induced senescence, recognized by increased SA-β-galactosidase activity, enhanced transcriptional activity of p53, and induction of the cell cycle inhibitors p21 and p27. Moreover, the peptide bound to p53 and competed with WT1 protein for binding to p53. WT1-pTj treatment led to sustained cell growth suppression, abrogation of clonogenicity and G2/M cell cycle arrest. Notably, in vivo studies showed that WT1-pTj inhibited both the metastases and subcutaneous growth of murine melanoma in syngeneic mice, and prolonged the survival of nude mice challenged with human melanoma cells. The 27-amino acid cell-penetrating WT1-derived peptide, depends on C3 and H16 for effective antimelanoma activity, inhibits proliferation of WT1-expressing human tumor cell lines, and may have an effective role in the treatment of WT1-expressing malignancies. |
topic |
Malignant melanoma Wilms tumor 1 (WT1) Senescence p53 |
url |
http://www.sciencedirect.com/science/article/pii/S2211546314000084 |
work_keys_str_mv |
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