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Metal nanoparticles (NPs), such as gold NPs (AuNPs), are particularly sensitive to X-rays, and thus specific accumulation of AuNPs in a tumor would allow radiotherapy with low energy X-rays and reduced side effects. AuNPs can be generated using HAuCl4 and the natural polyphenol epigallocatechin-3-gallate (EGCG) in the presence of citrate. Here, we generated EGCG-AuNPs in the presence of several additives and examined the accumulation of these NPs in mouse tumors following intravenous administration. EGCG-AuNPs 15 ​nm in diameter in the presence of sodium alginate accumulated more in tumors compared to 40-nm-diameter EGCG-AuNPs. Furthermore, the results of in vitro cellular uptake and serum protein absorption studies suggest that adsorption of 15–16 ​kDa serum proteins to EGCG-AuNPs suppresses accumulation in tumors. Thus, tendency to adsorb specific proteins on EGCG-AuNPs surface should be tailored for enhancing their accumulation in tumors.

Summary: Methionine addiction, found in all types of cancer investigated, is because of the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we compared the histone H3 lysine-methylation status and degree of malignancy between methionine-addicted cancer cells and their isogenic methionine-independent revertants, selected by their growth in low concentration of methionine. The methionine-independent revertans can grow on low levels of methionine or independently of exogenous methionine using methionine precursors, as do normal cells. In the methionine-independent revertants, the excess levels of trimethylated histone H3 lysine marks found in the methionine-addicted parental cancer cells were reduced or lost, and their tumorigenicity and experimental metastatic potential in nude mice were also highly reduced. Methionine addiction of cancer is linked with malignancy and hypermethylation of histone H3 lysines. The results of the present study thus provide a unique framework to further understand a fundamental basis of malignancy.

Purpose: Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, we investigated the reduced form of coenzyme Q10 (rCoQ10) as a potential radioprotector in a mouse model. Methods and Materials: rCoQ10 was added to a standard laboratory mouse diet at a final concentration of 1.0% 9 days before irradiation and 30 days thereafter or dissolved in corn oil and administered transorally. Accumulated amounts of coenzyme Q10 (CoQ10) or coenzyme Q9 in the intestine were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), apoptosis, and morphologic changes in the intestine were assessed by immunohistochemistry after administration of 13 Gy of x-ray to the mouse abdomen. Body weight and survival were monitored for 30 days after irradiation. Cytotoxicity using 3 human cancer cell lines and the tumor growth–inhibiting effect in a xenograft were investigated to determine whether rCoQ10 interferes with radiation-specific cytotoxic effects on tumor growth. Results: CoQ10 was greatly accumulated in all sections of the intestine after both massive transoral dosing and dietary administration, whereas coenzyme Q9 was not. Administration of rCoQ10 suppressed ROS production and inhibited apoptosis in the crypts, resulting in preservation of villi structures after irradiation. Notably, 92% of mice fed the rCoQ10-supplemented diet were healthy and alive 30 days after irradiation, whereas 50% of control mice died (P