Abstract
Current treatment options for castration-resistant
prostate cancer (CRPC) are limited. In this study, a
high-throughput screen of 4910 drugs and drug-like
molecules was performed to identify antiproliferative
compounds in androgen ablated prostate cancer cells. The
effect of compounds on cell viability was compared in
androgen ablated LNCaP prostate cancer cells and in LNCaP
cells grown in presence of androgens as well as in two
non-malignant prostate epithelial cells (RWPE-1 and
EP156T). Validation experiments of cancer specific
anti-proliferative compounds indicated pinosylvin methyl
ether (PSME) and tanshinone IIA as potent inhibitors of
androgen ablated LNCaP cell proliferation. PSME is a
stilbene compound with no previously described
anti-neoplastic activity whereas tanshinone IIA is
currently used in cardiovascular disorders and proposed
as a cancer drug. To gain insights into growth inhibitory
mechanisms in CRPC, genome-wide gene expression analysis
was performed in PSME- and tanshinone IIA-exposed cells.
Both compounds altered the expression of genes involved
in cell cycle and steroid and cholesterol biosynthesis in
androgen ablated LNCaP cells. Decrease in androgen
signalling was confirmed by reduced expression of
androgen receptor and prostate specific antigen in PSME-
or tanshinone IIA-exposed cells. Taken together, this
systematic screen identified a novel anti-proliferative
agent, PSME, for CRPC. Moreover, our screen confirmed
tanshinone IIA as well as several other compounds as
potential prostate cancer growth inhibitors also in
androgen ablated prostate cancer cells. These results
provide valuable starting points for preclinical and
clinical studies for CRPC treatment.
Original language | English |
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Pages (from-to) | 12-22 |
Journal | Journal of Molecular Biochemistry |
Volume | 5 |
Publication status | Published - 2016 |
MoE publication type | A1 Journal article-refereed |
Keywords
- cancer
- prostate cancer
- castration resistant
- high-throughput screen
- pinosylvin methyl ether
- tanshinone IIA