TY - JOUR
T1 - Sodium selenite inhibits interleukin-6-mediated androgen receptor activation in prostate cancer cells via upregulation of c-Jun
AU - Gazi, Mozammel H.
AU - Gong, Aiyu
AU - Donkena, Krishna V.
AU - Young, Charles Y.F.
N1 - Funding Information:
We thank Dr. Junxuan Lu of Hormel Institute for providing us with the MSeA compound. This work is supported by an NIH grant no. CA89000.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - Background: It has been suggested that interleukin-6 (IL-6) may modulate androgen receptor (AR) action to accelerate prostate cancer (PCa) progression. Selenium compounds are highly recommended as a promising chemopreventive agent for PCa. This study was to determine if selenium can repress IL-6 mediated AR action in PCa progression. Methods: Cell proliferation, prostate-specific antigen, gene transfer, and Western blot assays were used to study the effects of sodium selenite and methylseleninic acid on IL-6 mediated AR action on an AR expressing human prostate cancer cell line, LNCaP. Results: We found that sodium selenite, but not methylseleninic acid, significantly (p < 0.05) inhibited IL-6-induced trans-activating activity of AR and cell proliferation in LNCaP cells. Interestingly, although sodium selenite did not show effect on activation of both STAT3 and ERK1/2 in the presence of IL-6, an increased expression of c-Jun was detected in cells after treatment with sodium selenite. Indeed, we showed overexpression of c-Jun blocked IL-6-induced AR activation. Conclusions: Taken together, our results suggest that sodium selenite not methylseleninic acid can inhibit IL-6-mediated AR activation by increased c-Jun in LNCaP cells. Sodium selenite may be a proper selenium form for further testing its potency on intervening IL-6-mediated PCa progression.
AB - Background: It has been suggested that interleukin-6 (IL-6) may modulate androgen receptor (AR) action to accelerate prostate cancer (PCa) progression. Selenium compounds are highly recommended as a promising chemopreventive agent for PCa. This study was to determine if selenium can repress IL-6 mediated AR action in PCa progression. Methods: Cell proliferation, prostate-specific antigen, gene transfer, and Western blot assays were used to study the effects of sodium selenite and methylseleninic acid on IL-6 mediated AR action on an AR expressing human prostate cancer cell line, LNCaP. Results: We found that sodium selenite, but not methylseleninic acid, significantly (p < 0.05) inhibited IL-6-induced trans-activating activity of AR and cell proliferation in LNCaP cells. Interestingly, although sodium selenite did not show effect on activation of both STAT3 and ERK1/2 in the presence of IL-6, an increased expression of c-Jun was detected in cells after treatment with sodium selenite. Indeed, we showed overexpression of c-Jun blocked IL-6-induced AR activation. Conclusions: Taken together, our results suggest that sodium selenite not methylseleninic acid can inhibit IL-6-mediated AR activation by increased c-Jun in LNCaP cells. Sodium selenite may be a proper selenium form for further testing its potency on intervening IL-6-mediated PCa progression.
KW - Androgen independent growth
KW - IL-6
KW - Prostate cancer
KW - Selenium
KW - c-Jun
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U2 - 10.1016/j.cca.2007.01.031
DO - 10.1016/j.cca.2007.01.031
M3 - Article
C2 - 17346688
AN - SCOPUS:33947689632
SN - 0009-8981
VL - 380
SP - 145
EP - 150
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1-2
ER -