|Holmstrom, Alexandra -|
|Lei, K.Y. -|
|Cheng, Wen-Hsing -|
|Wu, Ryan -|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 7, 2011
Publication Date: September 1, 2012
Citation: Holmstrom, A., Zeng, H., Lei, K., Cheng, W., Wu, R. 2012. Nutritional and supranutritional levels of selenate differentially suppress prostate tumor growth in adult but not young nude mice. Journal of Nutritional Biochemistry. 23(9):1086-91. Interpretive Summary: Suboptimal Selenium (Se) intake has been implicated in viral infections, male infertility, depressed immunity, and higher risk of cancer incidence. Selenium is known to regulate carcinogenesis and immunity at nutritional and supranutritional levels, and a strong body of evidence indicates interactions among Se, cancer and immunity. In this study, we show that dietary selenate suppresses PC-3 cancer cell xenograft in nude mice in a manner depending on the stage of tumor development and Se doses. Dietary Se status does not affect levels of CD8+ and CD4+ T cells, but high level of dietary Se increases the expression of CD25+CD4+ T cells, an indicator of T cell activation. Taken together, dietary Se at the nutritional and supranutritional levels differentially regulates tumor development and T cell immunity in adult nude mice engrafted with PC-3 prostate cancer cells. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and cancer prevention.
Technical Abstract: Selenium (Se) is known to regulate carcinogenesis and immunity at nutritional and 26 supranutritional levels. Because the immune system provides critical defenses against 27 cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop 28 CD8+ and CD4+ T cells extrathymically, we asked whether dietary Se can modulate T cell 29 maturation and tomirigenesis in nude mice. Thirty homozygous nude mice were fed a 30 Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 31 (Se++) mg Se/kg (as Na2SeO4) for 6 months, followed by a 7-week time course of PC-3 32 prostate cancer cell xenograft (2 x 106 cells/site, 2 sites/mouse). Here, we show that the Se- 33 diet enhanced the initial tumor development on Day 11-17 whereas tumor growth was 34 suppressed with Se++ diet on Day 35-47 after the xenograft. Although dietary Se status did 35 not affect levels of CD4+ and CD8+ T cells during the time course as determined by flow 36 cytometric analyses, mice fed with the Se++ diet expressed increased amount of 37 CD25+CD4+ T cells on Day 9. Taken together, dietary Se at the nutritional and 38 supranutritional levels differentially regulate tumor development and T cell immunity in 39 adult nude mice engrafted with PC-3 prostate cancer cells.