Abstract
The epithelial–mesenchymal transition (EMT) is a molecular process connected to higher expression of vimentin and increased activity of transcription factors (Snail, Twist) which restrains E-cadherin. EMT has been linked to prostate cancer metastatic potential, therapy resistance, and poor outcomes. Kinetin riboside (9-(b-dribofuranosyl)-6-furfurylaminopurine, KR) is a naturally occurring cytokinin, which induces apoptosis and shows strong antiproliferative activity against various human cancer cell lines. To establish the effect of KR on human prostate cell lines, expression of, e.g. AR, E-, N-cadherins, Vimentin, Snail, Twist, and MMPs, was analysed at mRNA and protein levels using Western Blot and RT-PCR and/or RQ-PCR techniques. KR inhibited the growth of human prostate cancer cells, but also, to a small extent, of normal cells. This effect depended on the type of the cells and their androgen sensitivity. KR also decreased the level of p-Akt, which takes part in androgen signalling modulation. The antiapoptotic Bcl-2 protein was down-regulated in cancer cell lines, while that of Bax is up-regulated upon KR exposure. KR contributed to re-expression of the E-cadherin as well as to significant changes in cell migration. Taken together, our results indicate for the first time that KR can be proposed as a factor for signalling pathways regulation that participates in the inhibition of development of aggressive forms of prostate cancer, and may alter the approach to therapeutic interventions. We propose KR as a potent inhibitor of EMT in human prostate cells.
Highlights
According to the data provided by National Cancer Institute [1] in 2019, prostate cancer (PC) stands for 9.9% of all new cancer cases and is responsible for as many as 5.2% of all cancer deaths
Human prostate cell lines (American Type Culture Collection—ATCC, Manassas, Virginia, USA)—PZHPV-7 and RWPE-1, WPMY-1 as well as human prostate cancer cell lines (ATCC)—LNCaP, PC-3 and Du-145
Three different cell lines derived from normal prostate gland—RWPE-1, WPMY-1 and PZHPV, as well as three cell lines derived from PC with different characterisation—LNCaP, Du145 and PC-3 were used
Summary
One of the most commonly employed treatments for high-risk localised and locally advanced PC is androgen deprivation therapy (ADT) [2]. It is based on great dependence of PC development on androgen influence [3]. Failure of ADT defines a castration-resistant prostate cancer (CRPC), a tumour that grows independently of exogenous androgens. At molecular level, this transformation may involve different patterns such as androgen receptor (AR) gene mutation or amplification, changes in expression of AR coregulators, increased expression of steroidogenic enzymes, increase in signalling through pathways that activate AR
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