Skip to main content
NCBI home page
Journal of Gynecologic Oncology logoLink to Journal of Gynecologic Oncology
letter
. 2013 Jan 8;24(1):96–97. doi: 10.3802/jgo.2013.24.1.96

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

Jee Young Hwang 1,✉
PMCID: PMC3549514  PMID: 23346319

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.

Footnotes

No potential conflict of interest relevant to this article was reported.

References

  • 1.Park JS, Ryu JY, Jeon HK, Cho YJ, Park YA, Choi JJ, et al. The effects of selenium on tumor growth in epithelial ovarian carcinoma. J Gynecol Oncol. 2012;23:190–196. doi: 10.3802/jgo.2012.23.3.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Hoefig CS, Renko K, Kohrle J, Birringer M, Schomburg L. Comparison of different selenocompounds with respect to nutritional value vs. toxicity using liver cells in culture. J Nutr Biochem. 2011;22:945–955. doi: 10.1016/j.jnutbio.2010.08.006. [DOI] [PubMed] [Google Scholar]
  • 3.Willhite CC, Ferm VH, Zeise L. Route-dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters. Teratology. 1990;42:359–371. doi: 10.1002/tera.1420420405. [DOI] [PubMed] [Google Scholar]
  • 4.Qi Y, Fu X, Xiong Z, Zhang H, Hill SM, Rowan BG, et al. Methylseleninic acid enhances paclitaxel efficacy for the treatment of triple-negative breast cancer. PLoS One. 2012;7:e31539. doi: 10.1371/journal.pone.0031539. [DOI] [PMC free article] [PubMed] [Google Scholar]
J Gynecol Oncol. 2013 Jan 8;24(1):96–97. doi: 10.3802/jgo.2013.24.1.97
Jeong-Won Lee 1,✉

Reply to JY Hwang

Selenium compounds fall into two categories, organic and inorganic forms. The anticancer activity of selenium is dependent on its chemical form. In general, inorganic selenium compounds, such as selenate or selenite, are known to produce genotoxic effects, and are therefore not preferred for medicinal use especially at high doses. Organic selenium-containing compounds are better tolerated, but are different in their anticancer activity depending on their pharmacokinetic and pharmacodynamics properties. The metabolism of selenium to a monomethylated intermediate, methylselenol, is presumed necessary for the expression of anticancer activity [1-3]. Methylselenol is highly reactive and difficult to formulate. Stable precursors, such as methylselenocysteine or methylseleninic acid, or selenomethionine, which can be converted endogenously to methylselenol, are good selenium precursors for generating methylselenol, the active selenium metabolite that exhibit anticarcinogenic activity. Accumulating evidence suggests that organic selenium-containing compounds have better anticancer activity and are less toxic compared to inorganic selenium compounds. For these reasons, selenomethionine, presumably the major form of selenium in selenized yeast, is selected for the supplement used in SELECT trial. Despite the above advantage of organic selenium, inorganic selenium was also shown to have anticancer activity in prostate cancer [4].

In our study, we tried to evaluate the in vitro and in vivo effect of inorganic selenium (sodium selenite) on tumor growth and food intake in ovarian carcinoma using animal model [5]. Because we used the partially immunodeficient (nude) mice in this study, the results of in vivo study could be different in immune competent models if selenium compound have some effects on immune system. Until now, there are a number of potential mechanisms proposed for the anti-proliferative effects of selenium, including antioxidant effects, enhancement of immune function, stimulation of apoptosis, and induction of cell-cycle arrest [6]. However, there are no conclusive evidences for which selenium compound including inorganic or organic forms is better and which route of administration is effective in treating cancer cells. Further experiments for pharmacokinetics and cytotoxic effect of various selenium compounds should be required to confirm this result.

Footnotes

No potential conflict of interest relevant to this article was reported.

References

  • 1.Ip C. Lessons from basic research in selenium and cancer prevention. J Nutr. 1998;128:1845–1854. doi: 10.1093/jn/128.11.1845. [DOI] [PubMed] [Google Scholar]
  • 2.Ip C, Ganther HE. Activity of methylated forms of selenium in cancer prevention. Cancer Res. 1990;50:1206–1211. [PubMed] [Google Scholar]
  • 3.Ip C, Hayes C, Budnick RM, Ganther HE. Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res. 1991;51:595–600. [PubMed] [Google Scholar]
  • 4.Lee SO, Yeon Chun J, Nadiminty N, Trump DL, Ip C, Dong Y, et al. Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenograft accompanied by a decrease in the expression of androgen receptor and prostate-specific antigen (PSA) Prostate. 2006;66:1070–1075. doi: 10.1002/pros.20329. [DOI] [PubMed] [Google Scholar]
  • 5.Park JS, Ryu JY, Jeon HK, Cho YJ, Park YA, Choi JJ, et al. The effects of selenium on tumor growth in epithelial ovarian carcinoma. J Gynecol Oncol. 2012;23:190–196. doi: 10.3802/jgo.2012.23.3.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Dong Y, Zhang H, Hawthorn L, Ganther HE, Ip C. Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Res. 2003;63:52–59. [PubMed] [Google Scholar]

Articles from Journal of Gynecologic Oncology are provided here courtesy of Asian Society of Gynecologic Oncology & Korean Society of Gynecologic Oncology and Colposcopy

RESOURCES