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Mol Med Rep. 2018 Jul;18(1):945-957. doi: 10.3892/mmr.2018.9061. Epub 2018 May 23.

Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition.

Author information

1
Department Orthopedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.

Abstract

Prostate cancer is the second most commonly diagnosed malignancy and the sixth global primary cause of malignancy‑associated fatality. Increased invasiveness and motility in prostate cancer cells are associated with ubiquitin proteasome system‑regulated epithelial to mesenchymal transition (EMT). Impairment of the endoplasmic reticulum (ER) causes ER stress due to the accumulation of unfolded proteins and altered cell survival. In the current study, the effect and mechanism of matrine on cell apoptosis, viability, migration and invasion of human prostate cancer cells in vivo and in vitro through the unfolded protein response (UPR)/ER stress pathway were investigated. Matrine inhibited proteasomal chymotrypsin‑like (CT‑like) activity in the prostate carcinoma cellular proteasome. Upregulated vimentin and N‑cadherin and downregulated E‑cadherin were also observed in vitro and in vivo. In vitro analyses showed that matrine repressed cell motility, viability and invasion, arrested the cell cycle at the G0/G1 phase and induced prostate cancer cell apoptosis. Furthermore, matrine activated the UPR/ER stress signaling cascade in prostate cancer cells and tumor tissues of xenograft‑bearing nude mice. Results also demonstrated that the anti‑apoptotic protein Bcl‑2 was downregulated, the pro‑apoptotic protein Bak was upregulated and the cell growth and cell cycle‑related proteins c‑Myc, Cyclin B1, Cyclin D1 and CDK1 were downregulated. Moreover, matrine inhibited tumor growth and Ki‑67 expression in xenograft‑bearing nude mice. To the best of our knowledge, the present study indicated for the first time that matrine exerted marked anticancer functions in human prostate carcinoma in vivo and in vitro through activation of the proteasomal CT‑like activity inhibition mediated by the UPR/ER stress signaling pathway.

PMID:
29845238
PMCID:
PMC6059727
DOI:
10.3892/mmr.2018.9061
[Indexed for MEDLINE]
Free PMC Article

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