Effect of Dietary Methylseleninic Acid and Se-Methylselenocysteine on Carcinogen-Induced, Androgen-Promoted Prostate Carcinogenesis in Rats

Abstract

Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models. However, we have shown that daily oral bolus administration of next-generation selenium forms, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) at 3 mg Se/kg body weight, inhibits prostate carcinogenesis in the TRAMP and pten-deficient mouse models and In Vivo growth of human prostate cancer cells. Here, we determined whether these Se forms prevent prostate cancer in a chemically induced-androgen promoted carcinogenesis rat model in which SeMet was not preventive. WU rats were treated with methylnitrosourea, and one week later, slow-release testosterone implants when they were randomized to groups fed AIN-93M diet supplemented with 3 ppm selenium as MSeA or MSeC or control diet. Mean survival, tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) and the incidence of tumors confined to dorsolateral and/or anterior prostate were not statistically significantly different among the groups. Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.

Acknowledgments

This study was supported, in part, by the National Institutes of Health under grant R01 CA172169. The authors acknowledge the dedicated animal care staff at the University of Illinois at Chicago, in particular Mr. James M. Blaugh. The authors greatly appreciate the generous gift of synthetic Se-methylselenocysteine by Professor Julian Spallholz, Department of Nutrition, Texas Tech University, Lubbock, TX.

Author’s Contributions

Conception and design: M.C. Bosland, J. Lü

Development of methodology: M.C. Bosland, J. Lü

Acquisition of data: M.C. Bosland, M.J. Schlicht

Analysis and interpretation of data: M.C. Bosland, J. Lü, Y. Deng

Writing, review, and/or revision of the manuscript: M.C. Bosland, M.J. Schlicht, Y. Deng, J. Lü

Study supervision: M.C. Bosland

Disclosure Statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported in part by the National Institutes of Health under grant R01 CA172169.