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常见膳食补充剂(姜黄素、穿心莲内酯和柠檬烯)对 p53 功能正常结肠癌细胞辐射生物学反应的影响。

Influence of common dietary supplements (curcumin, andrographolide, and d-limonene) on the radiobiological responses of p53-competent colonic cancer epithelial cells.

机构信息

Radiation Sciences Graduate Program, McMaster University, Hamilton, Canada.

Department of Biology, McMaster University, Hamilton, Canada.

出版信息

Int J Radiat Biol. 2021;97(3):341-347. doi: 10.1080/09553002.2021.1864499. Epub 2021 Jan 7.

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.

摘要

目的

本研究的主要目的是确定市售常见膳食植物化学物补充剂(姜黄素、穿心莲内酯和柠檬烯)是否对 p53 功能正常的人结肠上皮细胞具有放射调节作用。

方法

采用集落形成实验研究植物化学物对培养的结肠上皮细胞(HCT116 p53)的直接照射或接受照射细胞条件培养基(旁观者效应)的影响。在直接照射中,包括化合物给药的预照射和后照射实验方案,分别作为定义放射防护和放射缓解作用的基础。在旁观者效应实验中,用植物化学物喂养供体细胞或受体细胞,定量评估旁观者诱导的集落形成细胞死亡。用 γ 源(Cs-137)进行 0.5-5 Gy 的剂量挑战。

结果

姜黄素、穿心莲内酯和柠檬烯似乎对 HCT116 p53 细胞没有放射防护和放射缓解作用。在照射后给药时发现柠檬烯可诱导放射增敏。这三种化合物似乎都不能调节 HCT116 p53 细胞中辐射诱导的旁观者信号产生和反应。

结论

姜黄素、穿心莲内酯和柠檬烯具有许多化学保护作用。本研究表明,它们不能保护结肠上皮细胞免受辐射杀伤。由于 HCT116 p53 细胞具有致瘤性,这一发现意味着这三种膳食化合物不会降低胃肠道肿瘤发生过程中辐射的杀伤效力。柠檬烯在照射后的放射增敏作用是一个值得进一步研究的有趣观察结果。

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