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

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.

Cytotoxic Profiling of Endogenous Metabolites Relevant to Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) on p53 Variant Human Colon Carcinoma Cell Lines.

Chemoprophylatic strategies against development of multifactorial diseases utilize compounds to block the multistep events in chronic inflammation and carcinogenesis. The successful chemopreventative candidate must therefore selectively inhibit growth of transformed cells and be administered frequently to confer maximal protection with minimal side effects. In addition to synthetic and exogenous natural compounds, endogenous metabolites represent another class of compounds that exhibit anticarcinogenic and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the endogenous metabolites-phenyl acetate, ursodeoxycholate, and tauroursodeoxycholate-to determine the role of p53-induced cytotoxicity, with p53 mutant and deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays, and macroscopic colony counts were used to quantify cell survival. The results demonstrate that the bile acids, ursodeoxycholate and tauroursodeoxycholate, exhibit selective cytotoxicity toward nonfunctional p53 cell lines suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, the tauroursodeoxycholate demonstrates high significance suggesting it might have practical uses in vivo.

Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines.

Chemoprevention strategies employ the use of compounds to inhibit the initiation, promotion, and progression phases of carcinogenesis. The successful chemopreventative candidate must therefore (1) selectively inhibit growth of transformed cells and (2) be administered on a frequent basis to confer maximal protection. Phytochemicals are a subclass of bioactive plant secondary metabolites that exhibit antioxidative, anticarcinogenic, and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the phytochemicals-curcumin, andrographolide, and d-limonene-to determine the role of p53-induced cytotoxicity, with p53-mutant and p53-deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays and macroscopic colony counts were used to quantify cell survival. The results demonstrate that each phytochemical exhibits selective cytotoxicity toward nonfunctional p53 cell lines, suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, only the d-limonene demonstrates considerable chemoprotection, suggesting it might have practical implications in vivo.