Department of Food Science and Biotechnology, Dongguk University, Seoul 10326, Korea.
StarlingForce Co., Ltd., Seoul 08511, Korea.
Biomolecules. 2020 Feb 18;10(2):324. doi: 10.3390/biom10020324.
2α-Hydroxyeudesma-4,11(13)-dien-8β,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from , 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.
2α-羟基莪术-4,11(13)-二烯-8β,12-内酯（HEDO），一种属于植物萜类化合物的大组倍半萜内酯，从 中分离出来，显示出体外对弥漫性大 B 细胞淋巴瘤细胞的细胞毒性活性。然而，抗癌作用的分子机制尚不清楚。在这项研究中，我们表明 HEDO 通过其增殖活性抑制淋巴瘤细胞系中的细胞生长并诱导细胞凋亡。HEDO 增加线粒体膜电位去极化并上调细胞内活性氧（ROS）。此外，我们检查了细胞周期效应，我们的结果提供了证据，表明细胞周期在 SubG0/G1 期的阻滞在阻止核因子-κB（NF-κB）信号传导中发挥重要作用，从而抑制 Ontario Cancer Institute（OCI）-LY3 淋巴瘤细胞的细胞生长。此外，HEDO 通过引发 Bcl-2 相关 X（BAX）和裂解的半胱天冬酶-3的激活诱导细胞凋亡，降低 B 细胞淋巴瘤 2（BCL2）、B 细胞淋巴瘤-额外大（BCL-XL）和前半胱天冬酶 3 的表达水平。基于这些发现，我们认为 HEDO 通过诱导 ROS 依赖性 SubG0/G1 阻滞和 OCI-LY3 细胞中的细胞凋亡具有作为淋巴瘤抗癌药物的潜力。
