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葫芦素 IIb,一种来自索诺拉南瓜的甾体三萜,对宫颈癌细胞和肺癌细胞具有抗增殖和促凋亡作用。

Cucurbitacin IIb, a steroidal triterpene from Ibervillea sonorae induces antiproliferative and apoptotic effects on cervical and lung cancer cells.

机构信息

Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora 83000, Mexico; Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora, Avenida Universidad e Irigoyen, Caborca, Sonora 83621, Mexico.

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia - Via del Liceo, 1, 06123 Perugia, Italy.

出版信息

Steroids. 2020 May;157:108597. doi: 10.1016/j.steroids.2020.108597. Epub 2020 Feb 14.

Abstract

Chemical studies on Ibervillea sonorae (S. Watson) Greene root led to isolation and chemical characterization of diverse cucurbitacin triterpenoid compounds such as kinoin A, B, C, and their glucosides. In previous studies, we demonstrated that kinoin A inhibits the cell proliferation on diverse cell line and induce apoptosis in HeLa cells. Therefore, the study of the isolated compounds from the extracts continued to be necessary. The objective of the present work was to isolate and chemically characterize the active compounds of the methanolic extract of the roots of I. sonorae and to evaluate their antiproliferative activity and induction of apoptosis. By chromatographic column separation and using NMR spectroscopy experiments, cucurbitacin IIb (CIIb), known as 23,24-dihydrocucurbitacin F or hemslecin B, was isolated and identified for the first time as a chemical constituent of the crude methanolic extract of this plant. The antiproliferative activity of CIIb was evaluated by MTT assay, and the apoptosis induction capacity was monitored by annexin V-FITC/propidium iodide using flow cytometry. CIIb showed a pronounced effect on the proliferation of HeLa and A549 tumor cells, with IC of 7.3 and 7.8 µM, respectively, but was less effective against L929 non-cancerous murine cell line. Apoptosis induction capacity of CIIb on HeLa and A549 was monitored by annexin V-FITC/propidium iodide using flow cytometry. Exposure of HeLa and A549 with CIIb (8 µM) for 24 h increased 56.9 and 52.3% respectively of the total apoptosis compared to the negative control (p < 0.005). CIIb, isolated for the first time from I. sonorae, showed antiproliferative activity against HeLa and A549 cell lines by inducing cell death by apoptosis.

摘要

对 Ibervillea sonorae(S. Watson)Greene 根的化学研究导致了多种葫芦素三萜化合物的分离和化学表征,如 kinoin A、B、C 及其糖苷。在以前的研究中,我们证明 kinoin A 抑制了多种细胞系的细胞增殖,并诱导了 HeLa 细胞的凋亡。因此,有必要继续研究从提取物中分离出的化合物。本工作的目的是从 I. sonorae 的根的甲醇提取物中分离和化学表征活性化合物,并评价其增殖抑制活性和诱导凋亡作用。通过色谱柱分离和使用 NMR 光谱实验,首次分离并鉴定出葫芦素 IIb(CIIb),也称为 23,24-二氢葫芦素 F 或 hemslecin B,为该植物粗甲醇提取物的化学成分。通过 MTT 测定法评估 CIIb 的增殖抑制活性,并通过流式细胞术使用 Annexin V-FITC/碘化丙啶监测凋亡诱导能力。CIIb 对 HeLa 和 A549 肿瘤细胞的增殖有明显的影响,IC 分别为 7.3 和 7.8 μM,但对非癌细胞系 L929 的作用较弱。通过流式细胞术使用 Annexin V-FITC/碘化丙啶监测 CIIb 对 HeLa 和 A549 的凋亡诱导能力。用 CIIb(8 μM)处理 HeLa 和 A549 24 h 后,与阴性对照相比,总凋亡分别增加了 56.9%和 52.3%(p<0.005)。CIIb 首次从 I. sonorae 中分离出来,通过诱导细胞凋亡导致细胞死亡,对 HeLa 和 A549 细胞系表现出增殖抑制活性。

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