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光动力疗法中的天然光敏剂:对人结肠腺癌SW480细胞单层和球体的体外活性

Natural photosensitizers in photodynamic therapy: In vitro activity against monolayers and spheroids of human colorectal adenocarcinoma SW480 cells.

作者信息

Cogno Ingrid Sol, Gilardi Pamela, Comini Laura, Núñez-Montoya Susana C, Cabrera Jose Luis, Rivarola Viviana Alicia

机构信息

Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, CP 5800 Río Cuarto, Córdoba, Argentina.

Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, CP 5800 Río Cuarto, Córdoba, Argentina.

出版信息

Photodiagnosis Photodyn Ther. 2020 Sep;31:101852. doi: 10.1016/j.pdpdt.2020.101852. Epub 2020 Jun 22.

Abstract

Photodynamic Therapy (PDT), is a treatment option for cancer.It involves the photochemical interaction of light, photosensitizer (PS) and molecular oxygen to produce radical species as well as singlet oxygen which induce cell death. Anthraquinones (AQs) have been extensively studied with respect to their UV/Vis absorption characteristics and their photosensitizing properties in photodynamic reactions. We study the photoactivity of different natural AQs (Parietin, Soranjidiol and Rubiadin) in treating monolayers and multicellular tumor spheroids (MCTSs). Rubiadin and soranjidiol were isolated and purified from the stem and leaves of Heterophyllae pustulata, and PTN was from the liquen Teloschistes flavicans by using repeated combination of several chromatographic techniques. Monolayer and spheroids of human colorectal adenocarcinoma SW480 cells were incubated with different concentrations of the AQs and then irradiated at room temperature. 24 h post-PDT cell viability, nuclear morphology and type of cell death were analyzed. We observed that Soranjidiol and Rubiadin showed no significant difference in the photosensitizing ability on monoculture of colon cancer cells (LD at 50 μM and 10 J/cm, for both AQs). Nevertheless, for Parietin (PTN) LD was achieved at (20 μM using the same light dose (10 J/cm). The death mechanism induced post-PDT was necrosis by use of Soranjidol and Rubiadin and apoptosis by use of PTN. Furthermore, in MCTSs of 300 and 900 μm, the treatment PTN- PDT produces the greatest cytotoxic effect. The three AQs analyzed could be promising chemotherapeutic candidates as anticancer PDT agents.

摘要

光动力疗法(PDT)是一种癌症治疗方法。它涉及光、光敏剂(PS)和分子氧之间的光化学相互作用,以产生自由基以及单线态氧,从而诱导细胞死亡。蒽醌(AQs)因其紫外/可见吸收特性及其在光动力反应中的光敏特性而受到广泛研究。我们研究了不同天然蒽醌(橙皮菌素、异橙黄酮和甲基异茜草素)在处理单层细胞和多细胞肿瘤球体(MCTSs)方面的光活性。异橙黄酮和甲基异茜草素是通过几种色谱技术的反复组合从异叶败酱的茎和叶中分离纯化得到的,而甲基橙皮苷则是从黄粉衣中提取得到的。将人结肠腺癌SW480细胞的单层细胞和球体与不同浓度的蒽醌一起孵育,然后在室温下进行照射。在光动力疗法后24小时分析细胞活力、细胞核形态和细胞死亡类型。我们观察到,异橙黄酮和甲基异茜草素在对结肠癌细胞单培养的光敏能力上没有显著差异(两种蒽醌在50μM和10 J/cm²时的半数致死剂量)。然而,对于甲基橙皮苷(PTN),在相同光剂量(10 J/cm²)下,20μM时达到半数致死剂量。光动力疗法后诱导的死亡机制,使用异橙黄酮和甲基异茜草素时为坏死,使用甲基橙皮苷时为凋亡。此外,在直径为300和900μm的多细胞肿瘤球体中,甲基橙皮苷 - 光动力疗法产生的细胞毒性作用最大。所分析的这三种蒽醌有望成为作为抗癌光动力疗法药物的有前途的化疗候选药物。

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