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沙丘植物中的次生代谢产物(精油)可诱导癌细胞产生细胞毒性作用。

Secondary metabolites (essential oils) from sand-dune plants induce cytotoxic effects in cancer cells.

机构信息

Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, HU6 7RX, UK.

University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.

出版信息

J Ethnopharmacol. 2020 Aug 10;258:112803. doi: 10.1016/j.jep.2020.112803. Epub 2020 Apr 3.

DOI:10.1016/j.jep.2020.112803
PMID:32251759
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Despite advances in modern therapeutic strategies, cancer remains the second leading cause of death worldwide. Therefore, there is a constant need to develop more efficient anticancer targeting strategies. The anticancer therapeutic proprieties of medicinal plants and their bioactive compounds have been reported for several years, making natural extracts and/or compounds derived from these a promising source of novel anticancer agents. Sand dune plants are subjected to severe environmental stresses, leading to the development of adaptations, including the production of secondary metabolites with a wide range of bioactivities, such as: anti-inflammatory, analgesic, antiseptic, hypoglycaemic, hypotensive, antinociceptive, antioxidant and anticancer.

AIM OF THE STUDY

The anticancer potential of sand dune plants remains under-investigated, so this research describes the characterisation of the composition of bioactive EOs from sand-dune plants of Peniche (Portugal), and assessment of their activity in vitro and potential mechanism of action.

MATERIALS AND METHODS

EOs were extracted from six sand-dune species of plants from Peniche sand dunes: Crithmum maritimum L., Seseli tortuosum L., Artemisia campestris subsp. maritima (DC.) Arcang., Juniperus phoenicea var. turbinata (Guss.) Parl., Otanthus maritimus (L.) Hoffmanns. & Link, and Eryngium maritimum L.. EOs composition was fully characterised chemically using Gas Chromatography-Mass Spectrometry (GC-MS). The assessment of anticancer activity and mechanism of action was performed in vitro using breast and colorectal cancer 2D and 3D spheroid cell line models, through cell proliferation assay, western blotting analysis, and cell cycle analysis.

RESULTS

EOs from the majority of the species tested (S. tortuosum, A. campestris subsp. maritima, O. maritimus, and E. maritimum) were mainly composed by hydrocarbon compounds (sequisterpenes and monoterpenes), showing antiproliferative activity in both 2D and 3D models. EO extracted from S. tortuosum and O. maritimus were identified as having the lowest IC values for both cell lines when compared with the other species tested. Furthermore, this antiproliferative activity was associated with increased p21 expression and induction of apoptosis.

CONCLUSIONS

The present study suggests that EOs extracted from S. tortuosum and O. maritimus present promising cytotoxic properties. Further evaluation of the extracts and their key components as potential anticancer agents should therefore be explored.

摘要

民族药理学相关性

尽管现代治疗策略取得了进展,但癌症仍然是全球第二大死亡原因。因此,需要不断开发更有效的抗癌靶向策略。多年来,药用植物及其生物活性化合物的抗癌治疗特性已被报道,使得天然提取物和/或源自这些植物的化合物成为新型抗癌药物的有前途的来源。沙丘植物受到严重的环境压力,导致适应的发展,包括产生具有广泛生物活性的次生代谢物,如:抗炎、镇痛、防腐、降血糖、降血压、抗伤害感受、抗氧化和抗癌。

研究目的

沙丘植物的抗癌潜力仍未得到充分研究,因此本研究描述了对来自葡萄牙彭西奇沙丘的沙丘植物的生物活性 EO 的组成进行表征,并评估了它们在体外的活性和潜在的作用机制。

材料和方法

从彭西奇沙丘的六种沙丘植物中提取 EO:滨海刺芹(Crithmum maritimum L.)、扭籽荠(Seseli tortuosum L.)、海滨滨藜(Artemisia campestris subsp. maritima(DC.)Arcang.)、桧柏(Juniperus phoenicea var. turbinata(Guss.)Parl.)、海滨山萝卜(Otanthus maritimus(L.)Hoffmanns. & Link)和滨海海罂粟(Eryngium maritimum L.)。使用气相色谱-质谱联用仪(GC-MS)对 EO 的化学成分进行全面化学表征。通过细胞增殖试验、western blotting 分析和细胞周期分析,在体外使用乳腺癌和结直肠癌细胞 2D 和 3D 球体细胞系模型评估抗癌活性和作用机制。

结果

在所测试的大多数物种(扭籽荠、海滨滨藜、海滨山萝卜和滨海海罂粟)的 EO 中,主要由碳氢化合物(倍半萜烯和单萜烯)组成,在 2D 和 3D 模型中均表现出增殖抑制活性。与其他测试的物种相比,从扭籽荠和海滨山萝卜中提取的 EO 被鉴定为对两种细胞系的 IC 值最低。此外,这种增殖抑制活性与 p21 表达的增加和细胞凋亡的诱导有关。

结论

本研究表明,从扭籽荠和海滨山萝卜中提取的 EO 具有有前途的细胞毒性特性。因此,应进一步评估提取物及其关键成分作为潜在抗癌药物的潜力。

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