Pharmacokinetics and cytotoxic effect of selenium compounds in rodent cancer xenograft model for therapy experiment

Abstract

To the editor: It has been, currently, acknowledged that selenium, as a chemopreventive agent, reduces considerably the risk of prostate, colorectal, lung, breast or any other cancer. Furthermore, therapeutic application of selenium compounds for several advanced epithelial carcinomas has been tried through translational research. Although the anti-tumor mechanism of selenium was not entirely understood, apoptosis mediated by reactive oxygen species is mainly suggested. In the volume 23, a research article regarding the therapeutic effects of sodium selenite on epithelial ovarian cancer was very impressive in terms of therapy experiment employing rodent orthotopic ovarian cancer xenograft model [1]. Summarizing the results, in vitro growth of selenite-treated cancer cells was significantly decreased; however, in vivo treatment with sodium selenite (1.5 mg/kg, intraperitoneal injection, 3 times per week) did not show apparent inhibitory effect against tumor growth. Various forms of selenium compounds exist. Selenomethionine is synthesized by plants and often used as a supplement in human studies. Selenocysteine represents the proteinogenic amino acid and selenium exerts its biological effects mainly via selenocysteine-containing proteins. Na2SeO3 (selenite), Na2SeO4 (selenate), and methylseleninic acid are inorganic selenium salts. From an in vitro assessment of cytotoxic effects on hepatocyte according to forms of selenium compounds, it was reported that the most powerful and fastest effect was observed in the methylseleninic acid, which is a potent second-generation selenium compound having different biological and pharmacological activity [2]. Additionally, in terms of route-dependent pharmacokinetics of selenium compounds, Willhite et al. [3] reported the high oral bioavailability of organic or inorganic selenium in hamsters. Total absorption of selenomethionine was measured as 73% and that of selenate was 100% in their experiment. Most recently, it was reported that the orally administered methylseleninic acid synergistically enhanced paclitaxel efficacy in a treatment experiment employing breast cancer xenograft model [4]. Therefore, these kinds of issues are needed to be considered for the future design of therapy experiment using selenium in ovarian cancer.