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一种源自新疆阿魏的晶型 lapiferin 通过诱导 MCF-7 乳腺癌细胞凋亡通路发挥抗癌作用。

A crystal lapiferin derived from Ferula vesceritensis induces apoptosis pathway in MCF-7 breast cancer cells.

机构信息

Cancer Biology Unit, Biochemistry Department, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Cairo, Egypt.

出版信息

Nat Prod Res. 2010 Feb;24(3):246-57. doi: 10.1080/14786410802685398.

Abstract

Ferula vesceritensis is a plant that is used in the traditional medicine in Algeria. Chromatographic investigation of the methylene chloride/methanol extract of the aerial parts of F. vesceritensis afforded a crystal carotene sesquiterpene designed lapiferin (10alpha-acetoxy-6alpha-angeloyloxy-8alpha,9alpha-epoxy-trans-caxotan-4beta-ol) for the first time from this species. The structure was determined by comprehensive NMR studies, including DEPT, COSY, NOE, HMQC, HMBC and HRMS, and X-ray data of lapiferin. We report here for the first time the isolation of lapiferin from F. vesceritensis as a new natural source, and we additionally report the first X-ray data for lapiferin. We also report for the first time the specific anti-cancer activity of lapiferin against human breast cancer cells (MCF-7), which is due to apoptosis and not necrosis. Moreover, we have identified for the first time the cell death pathway induced by lapiferin in human breast cancer cells, and also that lapiferin evokes multiple consequences that trigger apoptotic cell death, involving the enhancement of DNA fragmentation, the activation of caspases and the induction of histone acetylation in MCF-7 cells. In conclusion, we record here F. vesceritensis as a new natural source of lapiferin and its first X-ray analysis, and the promising specific anti-cancer activity against human breast cancer of lapiferin and accordingly F. vesceritensis extract.

摘要

新疆阿魏是一种在阿尔及利亚传统医学中使用的植物。对新疆阿魏地上部分的二氯甲烷/甲醇提取物进行色谱分析,首次从该种植物中得到结晶类胡萝卜素倍半萜 lapiferin(10α-乙酰氧基-6α-当归酰氧基-8α,9α-环氧-反式-caxotan-4β-醇)。通过全面的 NMR 研究,包括 DEPT、COSY、NOE、HMQC、HMBC 和 HRMS,以及 lapiferin 的 X 射线数据,确定了其结构。我们首次报道了 lapiferin 从新疆阿魏中的分离,作为一种新的天然来源,我们还首次报道了 lapiferin 的 X 射线数据。我们还首次报道了 lapiferin 对人乳腺癌细胞(MCF-7)的特异性抗癌活性,这是由于细胞凋亡而不是细胞坏死。此外,我们首次鉴定了 lapiferin 在人乳腺癌细胞中诱导的细胞死亡途径,并且还发现 lapiferin 引发了多种触发细胞凋亡的后果,包括增强 DNA 片段化、激活半胱天冬酶和诱导 MCF-7 细胞组蛋白乙酰化。总之,我们在这里记录了新疆阿魏作为 lapiferin 的一个新的天然来源及其首次 X 射线分析,以及 lapiferin 对人乳腺癌的有希望的特异性抗癌活性,因此新疆阿魏提取物也具有这种活性。

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