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石黄皮次生物质石黄酸的潜在抗癌活性。

Potential anticancer activity of lichen secondary metabolite physodic acid.

机构信息

Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, V.le A. Doria 6, 95125, Catania, Italy.

Department of Chemistry, University Técnica Federico Santa Maria, Casilla 110-V, Valparaìso, Chile.

出版信息

Chem Biol Interact. 2017 Feb 1;263:36-45. doi: 10.1016/j.cbi.2016.12.007. Epub 2016 Dec 21.

Abstract

Secondary metabolites present in lichens, which comprise aliphatic, cycloaliphatic, aromatic and terpenic compounds, are unique with respect to those of higher plants and show interesting biological and pharmacological activities. However, only a few of these compounds, have been assessed for their effectiveness against various in vitro cancer models. In the present study, we investigated the cytotoxicity of three lichen secondary metabolites (atranorin, gyrophoric acid and physodic acid) on A375 melanoma cancer cell line. The tested compounds arise from different lichen species collected in different areas of Continental and Antarctic Chile. The obtained results confirm the major efficiency of depsidones. In fact, depsides atranorin and gyrophoric acid, showed a lower activity inhibiting the melanoma cancer cells only at more high concentrations. Whereas the depsidone physodic acid, showed a dose-response relationship in the range of 6.25-50 μM concentrations in A375 cells, activating an apoptotic process, that probably involves the reduction of Hsp70 expression. Although the molecular mechanism, by which apoptosis is induced by physodic acid remains unclear, and of course further studies are needed, the results here reported confirm the promising biological properties of depsidone compounds, and may offer a further impulse to the development of analogues with more powerful efficiency against melanoma cells.

摘要

地衣中的次生代谢产物包括脂肪族、环脂族、芳香族和萜类化合物,与高等植物的次生代谢产物相比具有独特性,并表现出有趣的生物和药理活性。然而,只有少数这些化合物因其对各种体外癌症模型的有效性而得到评估。在本研究中,我们研究了三种地衣次生代谢产物(无羁萜、石耳酸和石耳酸)对 A375 黑色素瘤癌细胞系的细胞毒性。测试的化合物来自智利大陆和南极不同地区采集的不同地衣物种。获得的结果证实了去甲二萜的主要功效。事实上,去甲二萜无羁萜和石耳酸仅在更高浓度时才表现出抑制黑色素瘤癌细胞的较低活性。而去甲二萜石耳酸在 A375 细胞的 6.25-50μM 浓度范围内表现出剂量反应关系,激活了一种可能涉及 Hsp70 表达降低的凋亡过程。尽管石耳酸诱导细胞凋亡的分子机制尚不清楚,当然还需要进一步的研究,但这里报道的结果证实了去甲二萜化合物具有有前途的生物学特性,并可能为开发对黑色素瘤细胞更有效力的类似物提供进一步的动力。

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