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

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.

Keywords:

• Phytochemical
• curcumin
• andrographolide
• d-limonene
• radiation
• bystander effect

Disclosure statement

The authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.

Additional information

Funding

The research was supported by a Canada Research Chairs grant to CM [Grant Number: 950-221284], NSERC Collaborative Research and Development grant [CRDPJ484381-15] to CM, NSERC Discovery grant [RGPIN293153-12] to CS, and a CANDU Owners Group grant to CS and Bruce Power [Grant Number: CRDPJ484381-15].

Notes on contributors

Dusan Vukmirovic

Dusan Vukmirovic, PhD, graduated from the PhD program in Radiation Sciences at McMaster University.

Nguyen T. K. Vo

Nguyen T. K. Vo, PhD, held a postdoctoral fellowship in radiation biology in the Department of Biology at McMaster University. Currently, he is remote-teaching in the School of Interdisciplinary Science at McMaster University.

Colin Seymour

Colin Seymour, PhD, is a Professor of Radiobiology in the Department of Biology at McMaster University. His research interest is low dose radiation mechanisms including bystander effects and lethal mutations.

Dave Rollo

Dave Rollo, PhD, is a Professor in the Department of Biology at McMaster University. His research explores evolutionary theories based on integrated life history tradeoffs using the transgenic growth hormone mouse.

Carmel Mothersill

Carmel Mothersill, PhD, is a Professor and Canada Research Chair in Environmental Radiobiology at McMaster University. Her research interests include low dose radiation effects on plants and animals with a focus on non-targeted effects.