National Institute of Medicinal Materials, 3B Quang Trung Street, Hoankiem District, Hanoi, Viet Nam.
College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea; Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
Carbohydr Res. 2022 Sep;519:108613. doi: 10.1016/j.carres.2022.108613. Epub 2022 Jun 15.
In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.
在我们之前对越南药用植物的研究中,我们发现中华重楼的地上部分的乙醇提取物在 MCF-7 人癌细胞系中表现出体外细胞毒性作用。在这里,我们使用组合色谱分离从重楼地上部分的正丁醇提取物中分离出包括一种新的甾体糖苷(paripoloside A(3))和五种已知化合物在内的六种化合物。我们根据光谱数据(质子和碳-13 核磁共振、异核单量子相干、异核多键相关、相关光谱和高分辨电喷雾电离质谱数据)和化学反应,明确阐明了它们的结构。在分离出的化合物中,重楼皂苷 II(PSII)对 MCF-7 乳腺癌细胞的细胞毒性作用最强。有趣的是,PSII 显著增加了 p53、p21、p27 和 Bax 蛋白水平的表达,并显著抑制了 cyclin D1 和视网膜母细胞瘤蛋白的表达。这些数据表明 PSII 可能诱导 MCF-7 细胞中的 G1/S 期细胞周期停滞和细胞凋亡途径的发展。此外,还使用分子对接研究了 PSII 对 MCF-7 乳腺癌细胞的作用机制。总之,我们的研究结果表明,重楼中的分离化合物是有希望的乳腺癌抑制剂候选物。