Cargando…
Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells
BACKGROUND: Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. RESULTS: In MCF7 and ZR-75 b...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498523/ https://www.ncbi.nlm.nih.gov/pubmed/26148846 http://dx.doi.org/10.1186/s12943-015-0403-4 |
_version_ | 1782380636471820288 |
---|---|
author | De Amicis, Francesca Aquila, Saveria Morelli, Catia Guido, Carmela Santoro, Marta Perrotta, Ida Mauro, Loredana Giordano, Francesca Nigro, Alessandra Andò, Sebastiano Panno, Maria L. |
author_facet | De Amicis, Francesca Aquila, Saveria Morelli, Catia Guido, Carmela Santoro, Marta Perrotta, Ida Mauro, Loredana Giordano, Francesca Nigro, Alessandra Andò, Sebastiano Panno, Maria L. |
author_sort | De Amicis, Francesca |
collection | PubMed |
description | BACKGROUND: Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. RESULTS: In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy. CONCLUSIONS: Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0403-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4498523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44985232015-07-11 Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells De Amicis, Francesca Aquila, Saveria Morelli, Catia Guido, Carmela Santoro, Marta Perrotta, Ida Mauro, Loredana Giordano, Francesca Nigro, Alessandra Andò, Sebastiano Panno, Maria L. Mol Cancer Research BACKGROUND: Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. RESULTS: In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy. CONCLUSIONS: Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0403-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-07 /pmc/articles/PMC4498523/ /pubmed/26148846 http://dx.doi.org/10.1186/s12943-015-0403-4 Text en © De Amicis et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research De Amicis, Francesca Aquila, Saveria Morelli, Catia Guido, Carmela Santoro, Marta Perrotta, Ida Mauro, Loredana Giordano, Francesca Nigro, Alessandra Andò, Sebastiano Panno, Maria L. Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title | Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title_full | Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title_fullStr | Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title_full_unstemmed | Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title_short | Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells |
title_sort | bergapten drives autophagy through the up-regulation of pten expression in breast cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498523/ https://www.ncbi.nlm.nih.gov/pubmed/26148846 http://dx.doi.org/10.1186/s12943-015-0403-4 |
work_keys_str_mv | AT deamicisfrancesca bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT aquilasaveria bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT morellicatia bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT guidocarmela bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT santoromarta bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT perrottaida bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT mauroloredana bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT giordanofrancesca bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT nigroalessandra bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT andosebastiano bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells AT pannomarial bergaptendrivesautophagythroughtheupregulationofptenexpressioninbreastcancercells |