Abstract
2α-Hydroxyeudesma-4,11(13)-dien-8β,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from Inula britannica, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the molecular mechanism of the anticancer effect remains unclear. In this study, we showed that HEDO inhibits cell growth by inducing apoptosis in lymphoma cell lines through its antiproliferative activity. HEDO increases the depolarization of mitochondrial membrane potential and upregulated intracellular reactive oxygen species (ROS). Furthermore, we examined the cell cycle effect, and our results provided evidence that the arrest of the cell cycle at the SubG0/G1 phase plays an important role in the ability of HEDO to inhibit cell growth in Ontario Cancer Institute (OCI)-LY3 lymphoma cells by preventing nuclear factor-kappa B (NF-κB) signaling. In addition, HEDO induced apoptosis by instigating the activation of Bcl-2-associated X (BAX) and cleaved caspase-3, decreasing B-cell lymphoma 2 (BCL2), B-cell lymphoma-extra large (BCL-XL), and procaspase 3 expression levels. Based on these findings, we suggest that HEDO has potential as an anticancer drug of lymphoma by inducing ROS-dependent accumulation of SubG0/G1 arrest and apoptosis in OCI-LY3 cells.
Highlights
There are two major categories of lymphomas, namely Hodgkin lymphoma and non-Hodgkin lymphoma (NHL), which include a diverse set of lymphoid malignancies [1]
The ethanol extract of I. britannica flowers was subjected to Diaion HP-20 column chromatography and divided into three fractions (A–C) based on the results of thin-layer chromatography (TLC)
Fraction B was further chromatographed, leading to the isolation of a sesquiterpene lactone, which was identified as HEDO by comparing its physicochemical and spectral data to those in the literature (Figure 1) [17]
Summary
There are two major categories of lymphomas, namely Hodgkin lymphoma and non-Hodgkin lymphoma (NHL), which include a diverse set of lymphoid malignancies [1]. Diffuse large B-cell lymphoma (DLBCL) is one of the most common subtypes of NHL worldwide, comprising 30–40% of all newly diagnosed cases [2]. Gene expression profiling was used to identify three subtypes according to molecular heterogeneity: activated B cell-like (ABC), germinal center B cell-like (GCB), and primary mediastinal B cell lymphoma (PMBCL) subgroups [3,4,5]. The least curable is activated B cell-like DLBCL, necessitating the development of new treatment strategies for this disease. ABC-DLBCL is characterized by constitutive activation of the nuclear factor-κB (NF-κB) pathway [8]. Whereas an oncogenic role for constitutive classic NF-κB activity has been demonstrated in DLBCL, inhibitors that block the activation of the canonical or alternative NF-κB pathways of DLBCL have yet to be developed
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