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MERLOS RODRIGO, M. STRMISKA, V. HORÁČKOVÁ, E. BUCHTELOVÁ, H. MICHÁLEK, P. STIBOROVÁ, M. ECKSCHLAGER, T. ADAM, V. HEGER, Z.
Original Title
Sarcosine influences apoptosis and growth of prostate cells via cell-type specific regulation of distinct sets of genes
Type
journal article in Web of Science
Language
English
Original Abstract
Background Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells. Methods To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine. Microarray results were experimentally verified using semi-quantitative-RT-PCR, clonogenic assay, through testing of the susceptibility of cells pre-incubated with sarcosine to anticancer agents with different modes of actions (inhibitors of topoisomerase II, DNA cross-linking agent, antimicrotubule agent and inhibitor of histone deacetylases) and by evaluation of activation of executioner caspases 3/7. Results We identified that irrespective of the cell type, sarcosine stimulates up-regulation of distinct sets of genes involved in cell cycle and mitosis, while down-regulates expression of genes driving apoptosis. Moreover, it was found that in all cell types, sarcosine had pronounced stimulatory effects on clonogenicity. Except of an inhibitor of histone deacetylase valproic acid, efficiency of all agents was significantly (P < 0.05) decreased in sarcosine pre-incubated cells. Conclusions Our comparative study brings evidence that sarcosine affects not only metastatic PCa cells, but also their malignant and non-malignant counterparts and induces very similar changes in cells behavior, but via distinct cell-type specific targets.
Keywords
cell cycle; chemoresistance; microarray; prostate cancer; sarcosine
Authors
MERLOS RODRIGO, M.; STRMISKA, V.; HORÁČKOVÁ, E.; BUCHTELOVÁ, H.; MICHÁLEK, P.; STIBOROVÁ, M.; ECKSCHLAGER, T.; ADAM, V.; HEGER, Z.
Released
1. 2. 2018
ISBN
0270-4137
Periodical
PROSTATE
Year of study
78
Number
2
State
United States of America
Pages from
104
Pages to
112
Pages count
9
BibTex
@article{BUT142852, author="Miguel Ángel {Merlos Rodrigo} and Vladislav {Strmiska} and Eva {Horáčková} and Hana {Michálková} and Petr {Michálek} and Marie {Stiborová} and Tomáš {Eckschlager} and Vojtěch {Adam} and Zbyněk {Heger}", title="Sarcosine influences apoptosis and growth of prostate cells via cell-type specific regulation of distinct sets of genes", journal="PROSTATE", year="2018", volume="78", number="2", pages="104--112", doi="10.1002/pros.23450", issn="0270-4137" }