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石蒜科生物碱在皮肤癌治疗中的作用:对人角质形成细胞的光保护作用及对黑色素瘤细胞的抗增殖活性

Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells.

作者信息

Castaneda Carol, Bravo Karent, Cortes Natalie, Bedoya Janeth, de Borges Warley S, Bastida Jaume, Osorio Edison

机构信息

Universidad de Antioquia, Facultad de Ciencias Farmaceuticas y Alimentarias, Grupo de Investigacion en Sustancias Bioactivas, Medellin, Colombia.

Universidad de Ibague, Facultad de Ciencias Naturales y Matematicas, Ibague, Colombia.

出版信息

J Appl Biomed. 2023 Apr;21(1):36-47. doi: 10.32725/jab.2023.004. Epub 2023 Mar 31.

Abstract

Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.

摘要

皮肤癌具有很高的死亡率和治疗失败率。在本研究中,为了开发一种用于皮肤癌管理的多药联合策略,评估了从石蒜科植物中分离得到的几种生物碱组分和纯生物碱在黑色素瘤细胞中的选择性细胞毒性。此外,将紫外线B(UVB)刺激的角质形成细胞(HaCaT)暴露于通过气相色谱-质谱联用(GC-MS)表征的七种生物碱组分中,并测量细胞内活性氧(ROS)和白细胞介素-6(IL-6)的产生,以评估它们的光保护作用。高加索水仙(鳞茎)生物碱组分(20μg/ml)对黑色素瘤细胞的活力有明显影响,使其降低了45.7%,而不影响健康的角质形成细胞。该生物碱组分和水仙环素(均为2.5μg/ml)分别将UVB诱导的ROS产生抑制了31.6%和29.4%。尖瓣水仙(鳞茎)生物碱组分(10μg/ml)表现出最高的抗炎潜力,可使IL-6的产生减少90.8%。根据化学计量学分析,石蒜碱和水仙环素对UVB照射的HaCaT细胞具有光保护作用,可减弱ROS和IL-6的产生。这些结果表明,石蒜科生物碱在皮肤癌管理中具有光保护和治疗潜力,尤其是在低浓度时。

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