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Multimechanistic combination enhances selenium’s antiproliferative effect in prostate cancer cells (826.2)
Author(s) -
Li Xiuqi,
Manwaring Eliza,
Hopkins Tyler,
Worden Joseph,
Schille Colton,
Eggett Dennis,
Lawson John,
Christensen Merrill
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.826.2
Subject(s) - selenium , in vivo , in vitro , prostate cancer , chemistry , cancer , cancer cell , cell growth , sodium , pharmacology , cancer research , stereochemistry , biochemistry , biology , medicine , microbiology and biotechnology , organic chemistry
The anti‐cancer activity of selenium (Se) has been demonstrated by multiple in vitro and in vivo studies. However, none have sought to combine different forms of Se, with their varied mechanisms, to enhance Se’s chemopreventive efficacy. In this study, we hypothesized that systematically blending multiple forms of Se will produce a pleiotropic, multimechanistic combination that optimizes the in vitro growth inhibition of PC‐3 cells. In order to accomplish this, we first determined the IC50s of methylseleninic acid (MSA), sodium selenite, and Se nanoparticles (nano Se) via Alamar Blue proliferation assay. They were 5.0 μM, 14.0 μM, and 14.6 μM, respectively. We then utilized mixture designs and response surface methodology to direct our combination experiments: 10 combinations of MSA, sodium selenite, and nano Se were selected, each equaling 10 μM Se total. Experimental data of these 10 combinations were used to construct a polynomial model. This mathematical model predicted the optimum combination of the these Se compounds in inhibiting PC‐3 cell growth to be 4.1 μM of MSA, 5.1 μM of sodium selenite, and 0.8 μM of nano Se. These data provide proof of principle that combinations of different Se compounds exhibit greater chemopreventive efficacy than individual Se agents. Grant Funding Source : Supported by NIH CA122235 to MJC and BYU Cancer Research Center Fellowship to XL.