Cargando…
Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death
BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704516/ https://www.ncbi.nlm.nih.gov/pubmed/29179721 http://dx.doi.org/10.1186/s13046-017-0632-z |
_version_ | 1783281912137121792 |
---|---|
author | Granato, Marisa Gilardini Montani, Maria Saveria Santarelli, Roberta D’Orazi, Gabriella Faggioni, Alberto Cirone, Mara |
author_facet | Granato, Marisa Gilardini Montani, Maria Saveria Santarelli, Roberta D’Orazi, Gabriella Faggioni, Alberto Cirone, Mara |
author_sort | Granato, Marisa |
collection | PubMed |
description | BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very aggressive behavior, displaying constitutive activation of STAT3 as well as of other oncogenic pathways and harboring wtp53. METHODS: Cell death was assessed by trypan blue exclusion assay, FACS analysis as well as by biochemical studies. The latter were also utilized to detect the occurrence of autophagy and the molecular mechanisms leading to the activation of both processes by apigenin. FACS analysis was used to measure the intracellular ROS utilizing DCFDA. RESULTS: We show that apigenin induced PEL cell death and autophagy along with reduction of intracellular ROS. Mechanistically, apigenin activated p53 that induced catalase, a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival pathway in PEL, as assessed by p53 silencing. On the other hand, STAT3 inhibition by apigenin resulted in p53 activation, since STAT3 negatively influences p53 activity, highlighting a regulatory loop between these two pathways that modulates PEL cell death/survival. CONCLUSION: The findings of this study demonstrate that apigenin may modulate pro-apoptotic and pro-survival pathways representing a valid therapeutic strategy against PEL. |
format | Online Article Text |
id | pubmed-5704516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57045162017-12-05 Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death Granato, Marisa Gilardini Montani, Maria Saveria Santarelli, Roberta D’Orazi, Gabriella Faggioni, Alberto Cirone, Mara J Exp Clin Cancer Res Research BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very aggressive behavior, displaying constitutive activation of STAT3 as well as of other oncogenic pathways and harboring wtp53. METHODS: Cell death was assessed by trypan blue exclusion assay, FACS analysis as well as by biochemical studies. The latter were also utilized to detect the occurrence of autophagy and the molecular mechanisms leading to the activation of both processes by apigenin. FACS analysis was used to measure the intracellular ROS utilizing DCFDA. RESULTS: We show that apigenin induced PEL cell death and autophagy along with reduction of intracellular ROS. Mechanistically, apigenin activated p53 that induced catalase, a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival pathway in PEL, as assessed by p53 silencing. On the other hand, STAT3 inhibition by apigenin resulted in p53 activation, since STAT3 negatively influences p53 activity, highlighting a regulatory loop between these two pathways that modulates PEL cell death/survival. CONCLUSION: The findings of this study demonstrate that apigenin may modulate pro-apoptotic and pro-survival pathways representing a valid therapeutic strategy against PEL. BioMed Central 2017-11-28 /pmc/articles/PMC5704516/ /pubmed/29179721 http://dx.doi.org/10.1186/s13046-017-0632-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Granato, Marisa Gilardini Montani, Maria Saveria Santarelli, Roberta D’Orazi, Gabriella Faggioni, Alberto Cirone, Mara Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title_full | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title_fullStr | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title_full_unstemmed | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title_short | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
title_sort | apigenin, by activating p53 and inhibiting stat3, modulates the balance between pro-apoptotic and pro-survival pathways to induce pel cell death |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704516/ https://www.ncbi.nlm.nih.gov/pubmed/29179721 http://dx.doi.org/10.1186/s13046-017-0632-z |
work_keys_str_mv | AT granatomarisa apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath AT gilardinimontanimariasaveria apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath AT santarelliroberta apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath AT dorazigabriella apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath AT faggionialberto apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath AT cironemara apigeninbyactivatingp53andinhibitingstat3modulatesthebalancebetweenproapoptoticandprosurvivalpathwaystoinducepelcelldeath |