TY - JOUR
T1 - Pin1 inhibitor Juglone exerts anti-oncogenic effects on LNCaP and DU145 cells despite the patterns of gene regulation by Pin1 differing between these cell lines
AU - Kanaoka, Ryuhei
AU - Kushiyama, Akifumi
AU - Seno, Yasuyuki
AU - Nakatsu, Yusuke
AU - Matsunaga, Yasuka
AU - Fukushima, Toshiaki
AU - Tsuchiya, Yoshihiro
AU - Sakoda, Hideyuki
AU - Fujishiro, Midori
AU - Yamamotoya, Takeshi
AU - Kamata, Hideaki
AU - Matsubara, Akio
AU - Asano, Tomoichiro
N1 - Publisher Copyright:
© 2015 Kanaoka et al.
PY - 2015/6/3
Y1 - 2015/6/3
N2 - Background: Prostate cancer initially develops in an androgen-dependent manner but, during its progression, transitions to being androgen-independent in the advanced stage. Pin1, one of the peptidyl-prolyl cis/trans isomerases, is reportedly overexpressed in prostate cancers and is considered to contribute to accelerated cell growth, which may be one of the major factors contributing to their androgen-independent growth. Thus, we investigated how Pin1 modulates the gene expressions in both androgen-dependent and androgen-independent prostate cancer cell lines using microarray analysis. In addition, the effects of Juglone, a commercially available Pin1 inhibitor were also examined. Methods: Two prostate cancer cell-lines, LNCaP (androgen-dependent) and DU145 (androgenindependent), were treated with Pin1 siRNA and its effects on gene expressions were analyzed by microarray. Individual gene regulations induced by Pin1 siRNA or the Pin1 inhibitor Juglone were examined using RT-PCR. In addition, the effects of Juglone on the growth of LNCaP and DU145 transplanted into mice were investigated. Results: Microarray analysis revealed that transcriptional factors regulated by Pin1 differed markedly between LNCaP and DU145 cells, the only exception being that Nrf was regulated in the same way by Pin1 siRNA in both cell lines. Despite this marked difference in gene regulations, Pin1 siRNA and Juglone exert a strong inhibitory effect on both the LNCaP and the DU145 cell line, suppressing in vitro cell proliferation as well as tumor enlargement when transplanted into mice. Conclusions: Despite Pin1-regulated gene expressions differing between these two prostate cancer celllines, LNCaP (androgen-dependent) and DU145 (androgen-independent), Pin1 inhibition suppresses proliferation of both cell-lines. These findings suggest the potential effectiveness of Pin1 inhibitors as therapeutic agents for prostate cancers, regardless of their androgen sensitivity.
AB - Background: Prostate cancer initially develops in an androgen-dependent manner but, during its progression, transitions to being androgen-independent in the advanced stage. Pin1, one of the peptidyl-prolyl cis/trans isomerases, is reportedly overexpressed in prostate cancers and is considered to contribute to accelerated cell growth, which may be one of the major factors contributing to their androgen-independent growth. Thus, we investigated how Pin1 modulates the gene expressions in both androgen-dependent and androgen-independent prostate cancer cell lines using microarray analysis. In addition, the effects of Juglone, a commercially available Pin1 inhibitor were also examined. Methods: Two prostate cancer cell-lines, LNCaP (androgen-dependent) and DU145 (androgenindependent), were treated with Pin1 siRNA and its effects on gene expressions were analyzed by microarray. Individual gene regulations induced by Pin1 siRNA or the Pin1 inhibitor Juglone were examined using RT-PCR. In addition, the effects of Juglone on the growth of LNCaP and DU145 transplanted into mice were investigated. Results: Microarray analysis revealed that transcriptional factors regulated by Pin1 differed markedly between LNCaP and DU145 cells, the only exception being that Nrf was regulated in the same way by Pin1 siRNA in both cell lines. Despite this marked difference in gene regulations, Pin1 siRNA and Juglone exert a strong inhibitory effect on both the LNCaP and the DU145 cell line, suppressing in vitro cell proliferation as well as tumor enlargement when transplanted into mice. Conclusions: Despite Pin1-regulated gene expressions differing between these two prostate cancer celllines, LNCaP (androgen-dependent) and DU145 (androgen-independent), Pin1 inhibition suppresses proliferation of both cell-lines. These findings suggest the potential effectiveness of Pin1 inhibitors as therapeutic agents for prostate cancers, regardless of their androgen sensitivity.
UR - http://www.scopus.com/inward/record.url?scp=84934892555&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0127467
DO - 10.1371/journal.pone.0127467
M3 - Article
C2 - 26039047
AN - SCOPUS:84934892555
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0127467
ER -