Chen Yonghu, Zhu Fangying, Che Xianhua, Li Yanwei, Li Ning, Jiang Zhe, Li Xuezheng
Yanbian University Hospital, Yanbian University, Yanji, 133002, People's Republic of China.
Changchun Institute of Biological Products Co., Ltd, Changchun, 130012, People's Republic of China.
Cell Div. 2023 Nov 1;18(1):19. doi: 10.1186/s13008-023-00102-w.
Angelica acutiloba Kitagawa, a traditional medicinal herb of the Umbelliferae family, has been demonstrated to have anticancer activity. In this study, we investigated the anti-lung cancer effects of two compounds extracted from A. acutiloba flowers: kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE) and platanoside (PLA). MTT, cell colony formation, and cell migration (scratch) assays revealed that both KAE (100 μM) and PLA (50 μM and 100 μM) inhibited the viability, proliferation, and migration of A549 cells. Dichlorodihydrofluorescein diacetate assays showed that KAE and PLA also induced the generation of reactive oxygen species in A549 cells. Morphologically, A549 cells swelled and grew larger under treatment with KAE and PLA, with the most significant changes at 100 μM PLA. Fluorescence staining and measurement of lactate dehydrogenase release showed that the cells underwent pyroptosis with concomitant upregulation of interleukin (IL)-1β and IL-18. Furthermore, both KAE and PLA induced upregulation of NF-κB, PARP, NLRP3, ASC, cleaved-caspase-1, and GSDMD expression in A549 cells. Subsequent investigations unveiled that these compounds interact with NLRP3, augment NLRP3's binding affinity with ASC, and stimulate the assembly of the inflammasome, thereby inducing pyroptosis. In conclusion, KAE and PLA, two active components of A. acutiloba flower extract, had significant anti-lung cancer activities exerted through regulation of proteins related to the NLRP3 inflammasome pathway.
当归（Angelica acutiloba Kitagawa）是伞形科的一种传统草药，已被证明具有抗癌活性。在本研究中，我们研究了从当归花中提取的两种化合物：山奈酚-3-O-α-L-(4″-E-p-香豆酰基)-鼠李糖苷（KAE）和芹菜苷（PLA）的抗肺癌作用。MTT法、细胞集落形成实验和细胞迁移（划痕）实验表明，KAE（100 μM）以及PLA（50 μM和100 μM）均抑制A549细胞的活力、增殖和迁移。二氯二氢荧光素二乙酸酯实验表明，KAE和PLA还可诱导A549细胞中活性氧的产生。形态学上，用KAE和PLA处理后，A549细胞肿胀且体积增大，其中100 μM PLA处理时变化最为显著。荧光染色和乳酸脱氢酶释放量的测定表明，细胞发生了焦亡，同时白细胞介素（IL）-1β和IL-18上调。此外，KAE和PLA均诱导A549细胞中NF-κB、PARP、NLRP3、ASC、裂解的半胱天冬酶-1和GSDMD表达上调。随后的研究发现，这些化合物与NLRP3相互作用，增强NLRP3与ASC的结合亲和力，并刺激炎性小体的组装，从而诱导焦亡。总之，当归花提取物的两种活性成分KAE和PLA通过调节与NLRP3炎性小体途径相关的蛋白质发挥显著的抗肺癌活性。
