Abstract

Purpose

The main goal of the research was to determine whether commercially available common dietary phytochemical supplements (curcumin, andrographolide, and d-limonene) have radiomodulatory effects on p53-competent human colonic epithelial cells.

Methods

Clonogenic survival assays were used to characterize effects of the phytochemicals on cultured colonic epithelial cells (HCT116 p53^+/+) in direct irradiation or upon receipt of irradiated-cell conditioned media (for bystander effects). In direct irradiation, feeding regimen experiments included compound administration pre- and post-irradiation, which was used as a basis to define effects as radioprotective and radiomitigative, respectively. In the bystander effect experiments, either donor or recipient cell cultures were fed with the phytochemicals and bystander-induced clonogenic cell death was quantitatively evaluated. Dose challenge was in the range of 0.5 − 5 Gy using the gamma source (Cs-137).

Results

Curcumin, andrographolide, and d-limonene appeared to not exhibit radioprotective and radiomitigative properties in HCT116 p53^+/+ cells. D-limonene was found to induce radiosensitization in post-irradiation administration. All three compounds appeared not to modulate the radiation-induced bystander signal production and response in HCT116 p53^+/+ cells.

Conclusions

Curcumin, andrographolide, and d-limonene are known to have many chemoprotective benefits. This work shows that they, however, did not protect colonic epithelial HCT116 p53^+/+ cells from radiation killing. As HCT116 p53^+/+ cells are tumourigenic in nature, this finding implies that these three dietary compounds would not reduce the killing efficacy of radiation in gastrointestinal tumorigenesis. The post-irradiation radiosensitizing effect of d-limonene was an intriguing observation worth further investigation.

中文翻译：

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常见膳食补充剂（姜黄素、穿心莲内酯和 d-柠檬烯）对具有 p53 活性的结肠癌上皮细胞放射生物学反应的影响

摘要

目的

该研究的主要目标是确定市售的常见膳食植物化学补充剂（姜黄素、穿心莲内酯和 d-柠檬烯）是否对具有 p53 活性的人类结肠上皮细胞具有放射调节作用。

方法

克隆形成存活测定用于表征植物化学物质在直接照射或接受照射细胞条件培养基（旁观者效应）时对培养的结肠上皮细胞（HCT116 p53 ^+/+）的影响。在直接辐照中，喂养方案实验包括辐照前和辐照后的复合给药，这被用作分别定义辐射防护和辐射减缓效应的基础。在旁观者效应实验中，供体或受体细胞培养物被喂以植物化学物质，并定量评估旁观者诱导的克隆细胞死亡。使用伽马源 (Cs-137) 的剂量激发在 0.5 - 5 Gy 的范围内。

结果

姜黄素、穿心莲内酯和 d-柠檬烯似乎在 HCT116 p53 ^+/+细胞中不表现出辐射防护和辐射减缓特性。发现 D-柠檬烯在照射后给药时会诱发放射致敏作用。所有三种化合物似乎都不会调节 HCT116 p53 ^+/+细胞中辐射诱导的旁观者信号产生和反应。

结论

众所周知，姜黄素、穿心莲内酯和 d-柠檬烯具有许多化学保护作用。然而，这项工作表明，它们不能保护结肠上皮 HCT116 p53 ^+/+细胞免受辐射杀伤。由于 HCT116 p53 ^+/+细胞本质上具有致瘤性，这一发现意味着这三种膳食化合物不会降低辐射在胃肠道肿瘤发生中的杀伤功效。d-柠檬烯的辐照后放射增敏作用是一个值得进一步研究的有趣观察结果。