Yu Jinsong, Yang Han, Lv Chunliu, Dai Xiaowei
Department of Thyroid and Breast Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.
Key Laboratory of Thyroid Tumor Prevention and Treatment of Nanyang, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.
Drug Dev Res. 2022 Nov;83(7):1673-1682. doi: 10.1002/ddr.21986. Epub 2022 Sep 6.
Karanjin is a bioactive furanoflavonoid with various pharmacological activities including anticancer activities. However, the effect and the related mechanism of karanjin in breast cancer (BC) have not been revealed. The potential targets of karanjin and BC were predicted using SwissTargetPrediction and GeneCards databases, respectively. The overlapping targets between karanjin and BC were identified using the Venn diagram. DAVID database was used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. Cell viability, proliferation, and apoptosis were examined by MTT (3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-tetrazolium bromide), EdU (5-ethynyl-2'-deoxyuridine) incorporation, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labeling) assays, respectively. The protein levels were measured by western blot analysis. We screened out 28 overlapping targets between karanjin and BC. KEGG analysis showed that the targets of karanjin in BC were associated with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Karanjin inhibited cell viability and impeded the proliferative ability of BC cells. Moreover, karanjin treatment induced apoptosis in BC cells. Additionally, karanjin treatment blocked the PI3K/Akt signaling pathway and activation of the PI3K/Akt pathway reversed the antitumor effect of karanjin on BC cells. In conclusion, karanjin exerted antitumor activity in BC cells by regulating the PI3K/Akt signaling pathway.
羽扇豆宁是一种具有多种药理活性（包括抗癌活性）的生物活性呋喃黄酮。然而，羽扇豆宁在乳腺癌（BC）中的作用及相关机制尚未明确。分别使用瑞士靶点预测数据库（SwissTargetPrediction）和基因卡片数据库（GeneCards）预测羽扇豆宁和乳腺癌的潜在靶点。通过维恩图确定羽扇豆宁和乳腺癌之间的重叠靶点。利用DAVID数据库进行京都基因与基因组百科全书（KEGG）富集通路分析。分别通过MTT（3-(4,5-二甲基-2-噻唑基)-2,5-二苯基溴化四氮唑）、EdU（5-乙炔基-2'-脱氧尿苷）掺入和TUNEL（末端脱氧核苷酸转移酶介导的dUTP地高辛标记）试验检测细胞活力、增殖和凋亡情况。通过蛋白质印迹分析测定蛋白质水平。我们筛选出羽扇豆宁和乳腺癌之间的28个重叠靶点。KEGG分析表明，羽扇豆宁在乳腺癌中的靶点与磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）通路相关。羽扇豆宁抑制细胞活力并阻碍乳腺癌细胞的增殖能力。此外，羽扇豆宁处理可诱导乳腺癌细胞凋亡。另外，羽扇豆宁处理阻断了PI3K/Akt信号通路，而PI3K/Akt通路的激活逆转了羽扇豆宁对乳腺癌细胞的抗肿瘤作用。总之，羽扇豆宁通过调节PI3K/Akt信号通路在乳腺癌细胞中发挥抗肿瘤活性。
