Takahashi Naoki, Iguchi Tomoki, Nagamine Anju, Shirai Remina, Nagata Akihiro, Yamauchi Junji, Mimaki Yoshihiro
Department of Medicinal Pharmacognosy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Laboratory of Molecular Neurology, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
ACS Omega. 2023 Jan 6;8(2):2808-2830. doi: 10.1021/acsomega.2c07766. eCollection 2023 Jan 17.
To explore new candidates for anticancer agents from natural products, the underground parts of , commonly used as an ornamental plant, were investigated phytochemically. As a result, 16 undescribed steroidal glycosides (-) were obtained, and their structures were determined mainly by NMR spectroscopic analysis and chemical transformations. The cytotoxic activities of the isolated compounds (-) against SBC-3 human small-cell lung cancer cells, A549 human adenocarcinoma cells, and HL-60 human promyelocytic leukemia cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Compound , a bisdesmosidic furostanol glycoside, and , a bisdesmosidic spirostanol glycoside, were cytotoxic to all three cell lines with IC values ranging from 1.2 to 13 μM. As exhibited the most potent cytotoxicity against SBC-3 cells among the isolated compounds, its apoptosis-inducing activity toward SBC-3 cells was examined. Compound arrested SBC-3 cells at the G/M phase of the cell cycle and effectively induced apoptosis via an intrinsic pathway accompanied by the dissipation of membrane potential and morphological changes in mitochondria.
为了从天然产物中探索新型抗癌药物候选物,对通常用作观赏植物的[植物名称]的地下部分进行了植物化学研究。结果,获得了16种未描述的甾体糖苷(-),其结构主要通过核磁共振光谱分析和化学转化确定。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2-四氮唑溴盐(MTT)法评估了分离得到的化合物(-)对SBC-3人小细胞肺癌细胞、A549人腺癌细胞和HL-60人早幼粒细胞白血病细胞的细胞毒性活性。化合物[具体化合物名称1],一种双去氧糖呋甾烷醇糖苷,和[具体化合物名称2],一种双去氧糖螺甾烷醇糖苷,对所有三种细胞系均具有细胞毒性,IC值范围为1.2至13μM。由于[具体化合物名称1]在分离得到的化合物中对SBC-3细胞表现出最强的细胞毒性,因此检测了其对SBC-3细胞的凋亡诱导活性。化合物[具体化合物名称1]使SBC-3细胞停滞在细胞周期的G/M期,并通过内在途径有效诱导凋亡,伴随着膜电位的消散和线粒体的形态变化。