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).
OBJECTIVE
Epidemiological studies and prevention trials suggest selenium is a promising preventive agent for prostate cancer. Selenium-containing compounds inhibited the growth of prostate cancer cell lines including androgen sensitive LNCaP and androgen insensitive DU145 and PC3 cells in vitro. Previous study revealed a novel mechanism of selenium action in which selenium (methylseleninic acid (MSA)) markedly reduced androgen receptor (AR) signaling in prostate cancer cells, suggesting that selenium might act as an antiandrogen, which could serve as a therapeutic agent for prostate cancer. In this study, we tested whether selenium (methylselenocysteine (MSC)) affects tumor growth of human prostate cancer cells by targeting AR signaling in vivo.


METHODS
Prostate tumor xenografts were established in nude mice by co-inoculating LNCaP cells with Matrigel. The mice-bearing tumors were treated with or without MSC (100 microg/mouse/day) via intraperitoneal injection for 2 weeks. The effect of MSC on tumor growth, AR, and prostate-specific antigen (PSA) expression was examined.


RESULTS
Methylselenocysteine (MSC) significantly inhibited LNCaP tumor growth (P < 0.05). AR expression in tumor tissues and serum PSA levels were considerably decreased in MSC-treated mice compared to the vehicle controls.


CONCLUSIONS
Pharmacological dose of MSC inhibits the growth of LNCaP human prostate cancer in vivo accompanied by a decrease in the expression of AR and PSA. These findings suggest that selenium (MSC) can serve as a therapeutic agent aimed at disruption of AR signaling for prostate cancer.
Lee
Soo Ok
SO
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Yeon Chun
Jae
J
Nadiminty
Nagalakshmi
N
Trump
Donald L
DL
Ip
Clement
C
Dong
Yan
Y
Gao
Allen C
AC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016566:Organoselenium Compounds / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics*; D012643:Selenium / Q000494:pharmacology / Q000627:therapeutic use; D017279:Selenocysteine / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D016566:Organoselenium Compounds; D011944:Receptors, Androgen; D017279:Selenocysteine; D017430:Prostate-Specific Antigen; D012643:Selenium; D003545:Cysteine; C002979:selenomethylselenocysteine