Role of human selenium-binding protein 56 (hSP56) in selenium’s growth inhibitory action on human prostate cancer cells

Proc Amer Assoc Cancer Res, Volume 45, 2004 1394 Low levels of dietary selenium are associated with increased cancer risk, and selenium compounds have been shown to exhibit a chemopreventive effect for malignancies of several organs, including the prostate. Recently, it was reported that treatment with selenomethionine caused G1 arrest and 80% reduction in the S phase of LNCaP human prostate cancer cells, while no such effect was detected on another human prostate cancer cell line, PC-3 (Venkateswaran, V., L.H. Klotz, and N.E. Fleshner Cancer Research, 2002. 62:540). Interestedly, we had shown previously that the human selenium-binding protein gene hSP56, the human homologue of a rodent gene implicated in chemoresistance, is highly expressed in androgen-responsive LNCaP cells but not in androgen-nonresponsive PC-3 cells. This expression in LNCaP cells is reversibly down-regulated by androgen in vitro (Yang, M. and A. J. Sytkowski, Cancer Research, 1998. 58:3150,). Taken together, these data suggest that selenium modulation of prostate cancer cell growth may be mediated, at least in part, by hSP56. To test this hypothesis, we down-regulated the expression of hSP56 in LNCaP cells with siRNA and stably over-expressed it in PC-3 cells using a mammalian expression vector. The cells were then incubated in the absence or presence of selenium (seleno-DL-methionine, 50 μM) for 24, 48, or 72 h. Cell counts were performed in triplicates using a hemacytometer, with trypan blue exclusion to identify viable cells, and growth curves were generated for each cell line. Proliferation of LNCaP cells with down-regulated hSP56 after 48 h of selenium treatment was increased significantly over that of control LNCaP cells, indicating that selenium’s anti-proliferative effect was diminished as hSP56 expression was reduced. Conversely, the growth of PC-3 cells with up-regulated hSP56 was decreased substantially or inhibited virtually completely relative to control PC-3 cells after selenium treatment, indicating the selenium’s anti-proliferative effect was increased by up-regulating hSP56 expression. These data strongly suggest that hSP56 may mediate part or all selenium’s anti-proliferative action on these prostate cancer cells. Increasing hSP56 expression at the clinical level may prove effective in reducing the growth of prostate and other forms of cancer.