Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes

(1) Tomentosin is the most representative sesquiterpene lactone extracted by <i>I. viscosa.</i> Recently, it has gained particular attention in therapeutic oncologic fields due to its anti-tumor properties. (2) In this study, the potential anticancer features of tomentosin were evaluated...

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Autores principales: Patrizia Virdis, Irene Marchesi, Francesco Paolo Fiorentino, Rossana Migheli, Luca Sanna, Valentina Bordoni, Giorgio Pintore, Grazia Galleri, Maria Rosaria Muroni, Luigi Bagella, Claudio Fozza, Maria Rosaria De Miglio, Luigi Podda
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/bd5baa551e894006aa9844547c6bea88
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spelling oai:doaj.org-article:bd5baa551e894006aa9844547c6bea882021-11-25T18:10:30ZTomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes10.3390/life111111282075-1729https://doaj.org/article/bd5baa551e894006aa9844547c6bea882021-10-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1128https://doaj.org/toc/2075-1729(1) Tomentosin is the most representative sesquiterpene lactone extracted by <i>I. viscosa.</i> Recently, it has gained particular attention in therapeutic oncologic fields due to its anti-tumor properties. (2) In this study, the potential anticancer features of tomentosin were evaluated on human Burkitt’s lymphoma (BL) cell line, treated with increasing tomentosin concentration for cytotoxicity screening. (3) Our data showed that both cell cycle arrest and cell apoptosis induction are responsible of the antiproliferative effects of tomentosin and may end in the inhibition of BL cell viability. Moreover, a microarray gene expression profile was performed to assess differentially expressed genes contributing to tomentosin activity. Seventy-five genes deregulated by tomentosin have been identified. Downregulated genes are enriched in immune-system pathways, and PI3K/AKT and JAK/STAT pathways which favor proliferation and growth processes. Importantly, different deregulated genes identified in tomentosin-treated BL cells are prevalent in molecular pathways known to lead to cellular death, specifically by apoptosis. Tomentosin-treatment in BL cells induces the downregulation of antiapoptotic genes such as BCL2A1 and CDKN1A and upregulation of the proapoptotic PMAIP1 gene. (4) Overall, our results suggest that tomentosin could be taken into consideration as a potential natural product with limited toxicity and relevant anti-tumoral activity in the therapeutic options available to BL patients.Patrizia VirdisIrene MarchesiFrancesco Paolo FiorentinoRossana MigheliLuca SannaValentina BordoniGiorgio PintoreGrazia GalleriMaria Rosaria MuroniLuigi BagellaClaudio FozzaMaria Rosaria De MiglioLuigi PoddaMDPI AGarticletomentosinBurkitt lymphomaBCL2A1CDKN1APMAIP1ScienceQENLife, Vol 11, Iss 1128, p 1128 (2021)
institution DOAJ
collection DOAJ
language EN
topic tomentosin
Burkitt lymphoma
BCL2A1
CDKN1A
PMAIP1
Science
Q
spellingShingle tomentosin
Burkitt lymphoma
BCL2A1
CDKN1A
PMAIP1
Science
Q
Patrizia Virdis
Irene Marchesi
Francesco Paolo Fiorentino
Rossana Migheli
Luca Sanna
Valentina Bordoni
Giorgio Pintore
Grazia Galleri
Maria Rosaria Muroni
Luigi Bagella
Claudio Fozza
Maria Rosaria De Miglio
Luigi Podda
Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
description (1) Tomentosin is the most representative sesquiterpene lactone extracted by <i>I. viscosa.</i> Recently, it has gained particular attention in therapeutic oncologic fields due to its anti-tumor properties. (2) In this study, the potential anticancer features of tomentosin were evaluated on human Burkitt’s lymphoma (BL) cell line, treated with increasing tomentosin concentration for cytotoxicity screening. (3) Our data showed that both cell cycle arrest and cell apoptosis induction are responsible of the antiproliferative effects of tomentosin and may end in the inhibition of BL cell viability. Moreover, a microarray gene expression profile was performed to assess differentially expressed genes contributing to tomentosin activity. Seventy-five genes deregulated by tomentosin have been identified. Downregulated genes are enriched in immune-system pathways, and PI3K/AKT and JAK/STAT pathways which favor proliferation and growth processes. Importantly, different deregulated genes identified in tomentosin-treated BL cells are prevalent in molecular pathways known to lead to cellular death, specifically by apoptosis. Tomentosin-treatment in BL cells induces the downregulation of antiapoptotic genes such as BCL2A1 and CDKN1A and upregulation of the proapoptotic PMAIP1 gene. (4) Overall, our results suggest that tomentosin could be taken into consideration as a potential natural product with limited toxicity and relevant anti-tumoral activity in the therapeutic options available to BL patients.
format article
author Patrizia Virdis
Irene Marchesi
Francesco Paolo Fiorentino
Rossana Migheli
Luca Sanna
Valentina Bordoni
Giorgio Pintore
Grazia Galleri
Maria Rosaria Muroni
Luigi Bagella
Claudio Fozza
Maria Rosaria De Miglio
Luigi Podda
author_facet Patrizia Virdis
Irene Marchesi
Francesco Paolo Fiorentino
Rossana Migheli
Luca Sanna
Valentina Bordoni
Giorgio Pintore
Grazia Galleri
Maria Rosaria Muroni
Luigi Bagella
Claudio Fozza
Maria Rosaria De Miglio
Luigi Podda
author_sort Patrizia Virdis
title Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
title_short Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
title_full Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
title_fullStr Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
title_full_unstemmed Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
title_sort tomentosin a sesquiterpene lactone induces antiproliferative and proapoptotic effects in human burkitt lymphoma by deregulation of anti- and pro-apoptotic genes
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/bd5baa551e894006aa9844547c6bea88
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