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. 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.