Hong Taeyeon, Ham Jiyeon, Song Gwonhwa, Lim Whasun
Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Korea.
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Pharmaceutics. 2022 Mar 4;14(3):564. doi: 10.3390/pharmaceutics14030564.
Alpinumisoflavone is a prenylated isoflavonoid derived from the fruit and . Alpinumisoflavone has anticancer properties in a variety of cancer cells, including colorectal, esophageal, renal and hepatocellular carcinoma. However, its mechanisms and effects in ovarian cancer remain unexplored. Our findings indicate that alpinumisoflavone triggers anti-proliferation in 2D- and 3D-cultured human ovarian cancer (ES2 and OV90) cells, including a reduction in the proliferating cell nuclear antigen expression and sub-G1 phase arrest of the cell cycle. Both alpinumisoflavone-treated ES2 and OV90 cells exhibited an augmentation in late apoptotic cells and the depolarization of mitochondrial membrane potential (MMP). We also observed a decrease in respiratory chain activity in ovarian cancer cells, owing to lower energy output by the alpinumisoflavone. In addition, combining cisplatin (a chemotherapeutic drug used in several malignancies) with alpinumisoflavone boosted apoptosis in ES2 and OV90 cells via a reduction in cell proliferation, induction of late apoptotic cells, and depolarization of MMP. Furthermore, alpinumisoflavone also regulated the PI3K/AKT, MAPK and endoplasmic reticulum (ER) stress regulatory signaling pathways, leading to cell death in both ES2 and OV90 cells. In general, our findings verified that alpinumisoflavone inhibited ovarian cancer cell growth via mitochondrial malfunction.
高山槐黄酮是一种来源于果实的异戊烯基化异黄酮。高山槐黄酮在多种癌细胞中具有抗癌特性，包括结直肠癌、食管癌、肾癌和肝细胞癌。然而，其在卵巢癌中的作用机制和效果仍未得到探索。我们的研究结果表明，高山槐黄酮可在二维和三维培养的人卵巢癌（ES2和OV90）细胞中引发抗增殖作用，包括增殖细胞核抗原表达的降低和细胞周期的亚G1期停滞。经高山槐黄酮处理的ES2和OV90细胞均表现出晚期凋亡细胞增加以及线粒体膜电位（MMP）去极化。我们还观察到卵巢癌细胞的呼吸链活性降低，这是由于高山槐黄酮使能量输出减少所致。此外，将顺铂（一种用于多种恶性肿瘤的化疗药物）与高山槐黄酮联合使用，通过减少细胞增殖、诱导晚期凋亡细胞和MMP去极化，增强了ES2和OV90细胞的凋亡。此外，高山槐黄酮还调节PI3K/AKT、MAPK和内质网（ER）应激调节信号通路，导致ES2和OV90细胞死亡。总体而言，我们的研究结果证实，高山槐黄酮通过线粒体功能障碍抑制卵巢癌细胞生长。
