Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes
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
Affiliations
Patrizia Virdis
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Irene Marchesi
Kitos Biotech Srls, Porto Conte Ricerche, 07100 Sassari, Italy
Francesco Paolo Fiorentino
Kitos Biotech Srls, Porto Conte Ricerche, 07100 Sassari, Italy
Rossana Migheli
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Luca Sanna
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Valentina Bordoni
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Giorgio Pintore
Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy
Grazia Galleri
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Maria Rosaria Muroni
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Luigi Bagella
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Claudio Fozza
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Maria Rosaria De Miglio
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
Luigi Podda
Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
(1) Tomentosin is the most representative sesquiterpene lactone extracted by I. viscosa. 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.
