Song Jisoo, Ham Jiyeon, Park Sunwoo, Park Soo Jin, Kim Hee Seung, Song Gwonhwa, Lim Whasun
Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Institute of Animal Molecular Biotechnology, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Antioxidants (Basel). 2023 Jun 22;12(7):1324. doi: 10.3390/antiox12071324.
Alpinumisoflavone is an isoflavonoid extracted from the fruit and . It has various physiological functions, such as anti-inflammation, anti-proliferation, and apoptosis, in malignant tumors. However, the effect of alpinumisoflavone is still not known in chronic diseases and other benign reproductive diseases, such as endometriosis. In this study, we examined the cell death effects of alpinumisoflavone on the endometriosis cell lines, End1/E6E7 and VK2/E6E7. Results indicated that alpinumisoflavone inhibited cell migration and proliferation and led to cell cycle arrest, depolarization of mitochondria membrane potential, apoptosis, and disruption of calcium homeostasis in the endometriosis cell lines. However, the cellular proliferation of normal uterine epithelial cells was not changed by alpinumisoflavone. The alteration in Ca levels was estimated in fluo-4 AM-stained End1/E6E7 and VK2/E6E7 cells after alpinumisoflavone treatment with or without calcium inhibitor, 2-aminoethoxydiphenyl borate (2-APB). The results indicated that a combination of alpinumisoflavone and a calcium inhibitor reduced the calcium accumulation in the cytosol of endometriosis cells. Additionally, alpinumisoflavone decreased oxidative phosphorylation (OXPHOS) in the endometriotic cells. Moreover, protein expression analysis revealed that alpinumisoflavone inactivated AKT signaling pathways, whereas it increased MAPK, ER stress, and autophagy regulatory proteins in End1/E6E7 and VK2/E6E7 cell lines. In summary, our results suggested that alpinumisoflavone could be a promising effective management agent or an adjuvant therapy for benign disease endometriosis.
高山槐黄酮是一种从果实中提取的异黄酮。它具有多种生理功能，如在恶性肿瘤中具有抗炎、抗增殖和诱导凋亡的作用。然而，高山槐黄酮在慢性疾病和其他良性生殖疾病（如子宫内膜异位症）中的作用尚不清楚。在本研究中，我们检测了高山槐黄酮对子宫内膜异位症细胞系End1/E6E7和VK2/E6E7的细胞死亡效应。结果表明，高山槐黄酮抑制细胞迁移和增殖，导致细胞周期停滞、线粒体膜电位去极化、凋亡以及子宫内膜异位症细胞系中钙稳态的破坏。然而，高山槐黄酮对正常子宫上皮细胞的细胞增殖没有影响。在用或不用钙抑制剂2-氨基乙氧基二苯基硼酸（2-APB）处理高山槐黄酮后，通过fluo-4 AM染色的End1/E6E7和VK2/E6E7细胞评估钙水平的变化。结果表明，高山槐黄酮和钙抑制剂的组合减少了子宫内膜异位症细胞胞质溶胶中的钙积累。此外，高山槐黄酮降低了子宫内膜异位症细胞中的氧化磷酸化（OXPHOS）。此外，蛋白质表达分析显示，高山槐黄酮使AKT信号通路失活，而在End1/E6E7和VK2/E6E7细胞系中增加了MAPK、内质网应激和自噬调节蛋白。总之，我们的结果表明，高山槐黄酮可能是一种有前途的有效治疗药物或良性疾病子宫内膜异位症的辅助治疗药物。
