Faculty of Pharma-Sciences, Teikyo University, Tokyo, Japan.
Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
Sci Rep. 2024 Sep 18;14(1):21814. doi: 10.1038/s41598-024-68528-y.
Baicalin is a flavonoid extracted from Scutellaria baicalensis Georgi. As it has significant antitumor and apoptosis-inducing effects, baicalin may be useful as a lead compound in new antitumor drug development. However, as the pharmacological actions of baicalin have yet to be elucidated, we isolated its target protein, which was successfully identified as Annexin A2. Annexin A2 forms a heterotetramer with S100A10 protein, which plays an important role in the plasminogen activator system. The heterotetramer bound to tissue plasminogen activator (tPA) activates the conversion of plasminogen to plasmin and promotes the expression of STAT-3 and NF-κB, which are target genes involved in the development of cancer. Moreover, NF-κB and STAT-3 induce the expression of cell inhibitors of apoptotic proteins and inhibit apoptosis. To examine whether these antitumor and apoptosis-inducing effects of baicalin are mediated by Annexin A2, we prepared Annexin A2 knockdown HepG2 cells. We compared mRNA expression by RT-qPCR and apoptosis by caspase-3 activity assays in Annexin A2 knockdown HepG2 cells. The results showed that the antitumor and apoptosis-inducing effects of baicalin are mediated by Annexin A2. The results of this study suggest that agents capable of inhibiting Annexin A2 may be useful candidates for the development of novel antitumor agents.
黄芩苷是从黄芩中提取的一种黄酮类化合物。由于它具有显著的抗肿瘤和诱导细胞凋亡作用，黄芩苷可能作为开发新型抗肿瘤药物的先导化合物。然而，由于黄芩苷的药理作用尚未阐明，我们分离了其靶蛋白，成功鉴定为膜联蛋白 A2。膜联蛋白 A2 与 S100A10 蛋白形成异四聚体，在纤溶酶原激活系统中发挥重要作用。异四聚体与组织型纤溶酶原激活物（tPA）结合可激活纤溶酶原转化为纤溶酶，并促进 STAT-3 和 NF-κB 的表达，这是参与癌症发展的靶基因。此外，NF-κB 和 STAT-3 诱导凋亡抑制蛋白的表达并抑制细胞凋亡。为了研究黄芩苷的这些抗肿瘤和诱导细胞凋亡作用是否通过膜联蛋白 A2 介导，我们制备了膜联蛋白 A2 敲低 HepG2 细胞。我们通过 RT-qPCR 比较了 Annexin A2 敲低 HepG2 细胞中的 mRNA 表达，并通过 caspase-3 活性测定比较了细胞凋亡。结果表明，黄芩苷的抗肿瘤和诱导细胞凋亡作用是通过膜联蛋白 A2 介导的。这项研究的结果表明，能够抑制膜联蛋白 A2 的药物可能是开发新型抗肿瘤药物的候选药物。
