Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea.
Department of Microbiology, Pusan National University, Busan 46241, Korea.
Molecules. 2021 Nov 12;26(22):6845. doi: 10.3390/molecules26226845.
has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.
已在韩国被用作治疗关节痛、风湿和炎症的民间药物。然而，其抗淋巴瘤作用尚未被阐明。在这里，我们证明 提取物及其三种二萜类化合物可有效杀死 B 淋巴细胞瘤细胞。我们的体外和体内研究结果表明，大陆酸， 提取物中的一种主要二萜类化合物，对癌细胞具有特异性细胞毒性活性，而对正常的鼠细胞和组织没有伤害。从机制上讲，大陆酸抑制了抗凋亡 Bcl-2 家族成员（如 Mcl-1 和 Bcl-xL）的表达。它使线粒体膜电位解偶联，导致效应半胱天冬酶 3/7 活性的刺激，最终导致细胞死亡。有趣的是，该药物与罗氟司特具有治疗协同作用，罗氟司特是一种泛 PDE4 抑制剂，在最近的临床试验中已成功被重新用于治疗侵袭性 B 细胞恶性肿瘤。我们的研究结果表明， 提取物及其三种二萜类化合物具有抗癌活性。我们还证明了当与罗氟司特联合使用时，大陆酸对 B 淋巴细胞瘤细胞存活的协同抑制作用。综上所述，大陆酸可能对治疗 B 细胞淋巴瘤具有重要的潜力。
