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Authors Ling Z, Guan H, You Z, Wang C, Hu L, Zhang L, Wang Y, Chen S, Xu B, Chen M
Received 11 February 2018
Accepted for publication 27 March 2018
Published 11 May 2018 Volume 2018:11 Pages 2735—2743
DOI https://doi.org/10.2147/OTT.S165262
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Background: Prostate cancer (PCa) is one of the most common malignant diseases
among male patients. Although androgen deprivation therapy remains the main
treatment for PCa, most patients would inevitably progress to
castration-resistant PCa, which is the main cause of cancer-related deaths.
Thus, novel antitumor agents are urgently needed. Recent studies demonstrated
that aloperine (ALO) as a natural alkaloid showed antitumor effects in other
cancer types. However, the biological function and underlying mechanisms of ALO
in PCa have not been investigated.
Methods: PCa cell lines including LNCaP, PC3 and DU145 were cultured and
treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis
assay and cell cycle assay were conducted to assess the biological role of ALO.
In addition, a PCa subcutaneous xenograft mouse model was established to
evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We
further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved
caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO
treatment of PCa cells.
Results: ALO effectively inhibited the cell viability of PCa by inducing
cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis
in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein
kinases and activated cleaved caspase 3 while exerting antiproliferation
function through inducing apoptosis and cell cycle arrest in PCa cells.
Conclusion: Based on our findings, we conclude that ALO could suppress the
tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells,
which indicated that ALO could act as a novel therapeutic agent in treatment of
human PCa.
Keywords: aloperine, prostate cancer, proliferation, apoptosis, cell cycle