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

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 a...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0127467-e0127467
Main Authors: Kanaoka, Ryuhei, Kushiyama, Akifumi, Seno, Yasuyuki, Nakatsu, Yusuke, Matsunaga, Yasuka, Fukushima, Toshiaki, Tsuchiya, Yoshihiro, Sakoda, Hideyuki, Fujishiro, Midori, Yamamotoya, Takeshi, Kamata, Hideaki, Matsubara, Akio, Asano, Tomoichiro
Format: Article
Language:English
Subjects:
Androgens
Animals
Apoptosis
Biotechnology
Cancer
Cancer cells
Cell cycle
Cell growth
Cell Line, Tumor
Cell proliferation
Chemical compounds
Development and progression
DNA microarrays
Enlargement
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Gene regulation
Genes
Genetic aspects
Growth factors
Humans
Inhibitors
Internal medicine
Juglone
Male
Medicine
Metabolism
Metabolites
Mice
Mice, Nude
Naphthoquinones - pharmacology
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase - antagonists & inhibitors
Peptidylprolyl Isomerase - genetics
Peptidylprolyl Isomerase - metabolism
Pharmacology
Physiological aspects
Pin1 protein
Polymerase chain reaction
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Regulations
Science
siRNA
Transcription factors
Tumor cell lines
Tumorigenesis
Xenograft Model Antitumor Assays
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Summary: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. Two prostate cancer cell-lines, LNCaP (androgen-dependent) and DU145 (androgen-independent), 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. 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. Despite Pin1-regulated gene expressions differing between these two prostate cancer cell-lines, 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0127467