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新型纳米姜黄素对皮肤T细胞淋巴瘤的抗肿瘤作用

Antineoplastic effect of a novel nanosized curcumin on cutaneous T cell lymphoma.

作者信息

Trochopoulos Antonios G X, Zaharieva Maya M, Marinova Mirela H, Yoncheva Krasimira, Tibi Ivanka Pencheva-El, Berger Martin R, Konstantinov Spiro M

机构信息

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.

Department of Infectious Microbiology, Institute of Microbiology 'Stephan Angeloff', Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

出版信息

Oncol Lett. 2020 Dec;20(6):304. doi: 10.3892/ol.2020.12167. Epub 2020 Sep 29.

Abstract

Cutaneous T cell lymphomas (CTCLs) are a group of heterogeneous, life-threatening, extra-nodal and lymphoproliferative T cell neoplasms. Since chronic inflammation serves a key role in CTCL progression, curcumin, a natural pigment with proven anti-inflammatory and antineoplastic properties, as well as minimal toxicity, may be used as a therapeutic agent. In the present study, two formulations of curcumin (standard ethanolic and a PluronicP-123/F-127 micellar solution) were compared regarding their cytotoxic efficacy and speed of internalization in three CTCL cell lines, namely HuT-78, HH and MJ. In addition, the modulating effect of curcumin on selected proteins involved in the proliferation and progression of the disease was determined. The results indicated the superiority of the PluronicP-123/F-127 micellar curcumin over the standard ethanol solution in terms of cellular internalization efficiency as determined by spectrophotometric analysis. Notably, the presence of commonly used media components, such as phenol red, may interfere when interpreting the cytotoxicity of curcumin, due to their overlapping absorbance peaks. Therefore, it was concluded that phenol red-free media are superior over media with phenol red in order to correctly measure the cytotoxic efficacy and cell penetration of curcumin. Depending on the cell line, the IC values of micellar curcumin varied from 29.76 to 1.24 µΜ, with HH cells demonstrating the highest sensitivity. This cell line had the lowest expression levels of the Wilms' tumor-1 transcription factor. Performing western blot analyses of treated and untreated CTCL cells, selective signal transduction changes were recorded for the first time, thus making curcumin nano-formulation an attractive and prospective option with therapeutic relevance for CTCL as a rare orphan disease.

摘要

皮肤T细胞淋巴瘤(CTCL)是一组异质性、危及生命、结外性和淋巴细胞增殖性T细胞肿瘤。由于慢性炎症在CTCL进展中起关键作用,姜黄素作为一种具有已证实的抗炎和抗肿瘤特性且毒性极小的天然色素,可作为一种治疗剂。在本研究中,比较了姜黄素的两种制剂(标准乙醇制剂和普朗尼克P-123/F-127胶束溶液)在三种CTCL细胞系,即HuT-78、HH和MJ中的细胞毒性效力和内化速度。此外,还确定了姜黄素对参与该疾病增殖和进展的选定蛋白质的调节作用。结果表明,通过分光光度分析测定,普朗尼克P-123/F-127胶束姜黄素在细胞内化效率方面优于标准乙醇溶液。值得注意的是,由于常用培养基成分(如酚红)的吸光度峰重叠,在解释姜黄素的细胞毒性时可能会产生干扰。因此,得出的结论是,无酚红培养基在正确测量姜黄素的细胞毒性效力和细胞穿透性方面优于含酚红培养基。根据细胞系的不同,胶束姜黄素的IC值在29.76至1.24μM之间变化,HH细胞表现出最高的敏感性。该细胞系中威尔姆斯瘤1转录因子的表达水平最低。对经处理和未处理的CTCL细胞进行蛋白质印迹分析,首次记录到选择性信号转导变化,从而使姜黄素纳米制剂成为一种对CTCL这种罕见孤儿病具有治疗相关性的有吸引力且有前景的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/470e/7573878/3506325a814d/ol-20-06-12167-g00.jpg

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