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Suppressed epithelial-mesenchymal transition and cancer stem cell properties
mediate the anti-cancer effects of ethyl pyruvate via regulation of the
AKT/nuclear factor-?B pathway in prostate cancer cells
#MMPMID30008929
Huang B
; Lv DJ
; Wang C
; Shu FP
; Gong ZC
; Xie T
; Yu YZ
; Song XL
; Xie JJ
; Li S
; Liu YM
; Qi H
; Zhao SC
Oncol Lett
2018[Aug]; 16
(2
): 2271-2278
PMID30008929
show ga
Castration-resistant prostate cancer (CRPC) is a leading cause of mortality among
cases of prostate cancer (PCa). Current treatment options for CRPC are limited.
Ethyl pyruvate (EP), a lipophilic derivative of pyruvic acid, has been reported
to have antitumor activities. In the present study, the efficacy of EP against
PCa was investigated using two human PCa cell lines and a mouse xenograft tumor
model. PC3 and CWR22RV1 cells were treated with EP, and cytotoxicity was
evaluated via Cell Counting Kit-8 and colony formation assays, while cell cycle
distribution was assessed by flow cytometry. Changes in cell migration and
invasion caused by EP treatment were also evaluated with Transwell and wound
healing assays, and changes in the expression of intracellular signaling pathway
components were detected by western blotting. EP treatment reduced cell
viability, induced G1 arrest, and activated the intrinsic apoptosis pathway.
Additionally, the in vivo experiments revealed that EP administration markedly
inhibited tumor growth. EP also reversed epithelial-mesenchymal transition and
suppressed cancer stem cell properties in part through negative regulation of
AKT/nuclear factor-?B signaling. These results indicate that EP has anticancer
activity in vitro and in vivo, and is therefore a promising therapeutic agent for
the treatment of PCa.